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Shi Y, Wang X, Pei Z, Shi H, Zhang Y, Yi T, Mei J, Guo Y, Dong Y, Ma T, Zhang Q, Jia X, Zhu Z, Xu S, Liu Y, Niu H, Jiang W, Jiang X, Zhou S, Sun L. Telpegfilgrastim for chemotherapy-induced neutropenia in patients with non-small cell lung cancer: a multicentre, randomized, phase 3 study. BMC Cancer 2025; 25:490. [PMID: 40098083 PMCID: PMC11916207 DOI: 10.1186/s12885-025-13736-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 02/14/2025] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND Chemotherapy-induced neutropenia (CIN) is usually managed by recombinant human granulocyte colony stimulating factor (rhG-CSF) and pegylated rhG-CSF (PEG-rhG-CSF). This study evaluated the efficacy and safety of telpegfilgrastim, a novel Y-shaped PEG-rhG-CSF, for CIN prophylaxis in patients with non-small cell lung cancer (NSCLC). METHODS This was a multicentre, randomized, open-label, active-controlled non-inferiority study. Patients with NSCLC who received 1-4 chemotherapy cycles of docetaxel plus carboplatin were randomized 1:1:1 to receive telpegfilgrastim 2 mg, 33 µg/kg or control drug (rhG-CSF [Topneuter®] in cycle 1 of chemotherapy, rhG-CSF [Topneuter®] or PEG-rhG-CSF [Xinruibai®] per patients' choice in cycles 2-4 of chemotherapy). The primary endpoint was duration of grade 4 neutropenia in cycle 1 of chemotherapy. Secondary endpoints included duration of grade 4 neutropenia in cycles 2-4 of chemotherapy, incidence of febrile neutropenia (FN), duration and incidence of ≥ grade 3 neutropenia, dynamic change of absolute neutrophil count from baseline and safety. RESULTS From October 16, 2020, to September 1, 2021, 133 patients were randomized to telpegfilgrastim 2 mg (n = 44), 33 µg/kg (n = 45) and control group (n = 44). In cycle 1 of chemotherapy, the mean duration of grade 4 neutropenia in telpegfilgrastim 2 mg, 33 µg/kg groups and control group were 0.02 day, 0.09 day and 0.16 day, respectively. The least square mean differences versus control group were -0.14 day [95% confidence interval [CI]: -0.35, 0.06] for telpegfilgrastim 2 mg group and -0.06 day [95% CI: -0.26, 0.15] for telpegfilgrastim 33 µg/kg group. which met the prespecified non-inferiority margin of 1 day. Incidence of grade 4 neutropenia, incidence of FN and duration of ≥ grade 3 neutropenia in cycles 1-4 of chemotherapy was similar between telpegfilgrastim groups and control group. Telpegfilgrastim was well tolerated, and the incidence of adverse events were comparable with control group. CONCLUSION This study demonstrated that telpegfilgrastim 2 mg or 33 μg/kg was non-inferior to rhG-CSF (Topneuter®) and PEG-rhG-CSF (Xinruibai®) for the management of CIN in patients with NSCLC. In particular, a 2 mg fixed dose of telpegfilgrastim presents a more convenient administration option. TRIAL REGISTRATION NCT04466137 , July 10, 2020.
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Affiliation(s)
- Yuankai Shi
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs, Beijing, China.
| | - Xinshuai Wang
- Department of Oncology, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China
| | - Zhidong Pei
- Department of Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, China
| | - Huaqiu Shi
- Department of Oncology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Yanjun Zhang
- Department of Oncology, Shaanxi Provincial Cancer Hospital, Xi'an, China
| | - Tienan Yi
- Department of Oncology, Xiangyang Central Hospital, Hubei University of Art and Science, Xiangyang, China
| | - Jiazhuan Mei
- Department of Oncology, Zhengzhou People's Hospital, Zhengzhou, China
| | - Yanzhen Guo
- Department of Oncology, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China
| | - Youhong Dong
- Department of Oncology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, China
| | - Tianjiang Ma
- Department of Oncology, Luohe Central Hospital, Luohe, China
| | - Qingyuan Zhang
- Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xiaojing Jia
- Department of Oncology, The Second Hospital of Jilin University, Changchun, China
| | - Zhengqiu Zhu
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Shen Xu
- Department of Medical Oncology, Zhangzhou Municipal Hospital of Fujian Province, Zhangzhou, China
| | - Yanyan Liu
- Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Hongrui Niu
- Department of Oncology, The First Affiliated Hospital of Xinxiang Medial University, Xinxiang, China
| | - Weimei Jiang
- Department of Oncology, The Second People's Hospital of Lianyungang, Lianyungang, China
| | - Xiaodong Jiang
- Department of Oncology, The First People's Hospital of Lianyungang, Lianyungang, China
| | - Shengyu Zhou
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study On Anticancer Molecular Targeted Drugs, Beijing, China
| | - Li Sun
- Xiamen Amoytop Biotech Co., LTD, Xiamen, China
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Skoulidis F, Li BT, Hochmair M, Govindan R, Vincent M, van der Wekken AJ, Reguart Aransay N, O’Byrne KJ, Girard N, Griesinger F, Nishio M, Häfliger S, Lindsay C, Reinmuth N, Paulus A, Papakotoulas P, Kim SW, Ferreira CG, Pasello G, Duruisseaux M, Gennatas S, Dimou A, Mehta B, Kormany W, Nduka C, Sylvester BE, Ardito-Abraham C, Wang Y, de Langen AJ. Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer. Oncologist 2025; 30:oyae356. [PMID: 39846981 PMCID: PMC11756274 DOI: 10.1093/oncolo/oyae356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 11/07/2024] [Indexed: 01/30/2025] Open
Abstract
INTRODUCTION We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks. METHODS Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0. Adverse events were deemed sotorasib-related per investigator causality assessment. RESULTS In the pooled population (n = 549), TRAEs were reported in 388 (70.7%) patients (grade 1: 124 [22.6%]; grade 2: 117 [21.3%]; grade ≥ 3: 147 [26.8%]). Gastrointestinal and hepatic TRAEs, including diarrhea (171 [31.1%]), nausea (80 [14.6%]), elevated alanine aminotransferase (ALT; 68 [12.4%]), and elevated aspartate aminotransferase (AST; 67 [12.2%]) were the most common (≥10%). Dose interruption and dose reduction of sotorasib resulted in the resolution of >90% of diarrhea events; median time to resolution were 18.0 days and 22.0 days, respectively. Similar trends were observed for elevated ALT and AST events. Patients who stopped immunotherapy <3 months before initiating sotorasib had a higher incidence of treatment-related hepatotoxicity (80/240 [33.3%]) than those who stopped immunotherapy ≥3 months before initiating sotorasib (26/188 [13.8%]). Treatment-related pneumonitis/interstitial lung disease (ILD) and corrected QT (QTc) prolongation were observed in 9 (1.6%) and 4 (0.7%) patients, respectively. Two (0.4%) patients died with TRAEs, 1 with ILD whose ultimate cause of death was disease progression, and the other with an unknown cause. CONCLUSIONS Sotorasib has a well-characterized safety profile in patients with KRAS G12C-mutated advanced NSCLC, and key risks are manageable with dose modification.
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Affiliation(s)
- Ferdinandos Skoulidis
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Bob T Li
- Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States
| | - Maximilian Hochmair
- Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, 1210 Vienna, Austria
| | - Ramaswamy Govindan
- Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
| | - Mark Vincent
- London Health Sciences Centre, Victoria Hospital, London, ON N6A 5W9, Canada
| | - Anthonie J van der Wekken
- Department of Pulmonary Diseases and Tuberculosis, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, the Netherlands
| | - Noemi Reguart Aransay
- Medical Oncology Department, Thoracic Oncology Unit Hospital Clinic, IDIBAPS, University of Barcelona, Villarroel, 08036 Barcelona, Spain
| | - Kenneth J O’Byrne
- Faculty of Health, Queensland University of Technology, Brisbane, QLD 4000, Australia
| | - Nicolas Girard
- Institut du Thorax Curie-Montsouris, Institut Curie, 75014 Paris, France
| | - Frank Griesinger
- Pius-Hospital Oldenburg, Department of Haematology and Oncology, University Department Internal Medicine-Oncology, University Medicine Oldenburg, 26121 Oldenburg, Germany
| | - Makoto Nishio
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan
| | - Simon Häfliger
- Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Colin Lindsay
- Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, United Kingdom
- The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Niels Reinmuth
- Department of Oncology, Asklepios Lung Clinic, German Center for Lung Research, Munich-Gauting, 82131 Gauting, Germany
| | - Astrid Paulus
- Department of Respiratory Medicine, University Hospital (CHU) of Liège, 4000 Liège, Belgium
| | - Pavlos Papakotoulas
- First Department of Clinical Oncology, Theageneio Cancer Hospital, 54639 Thessaloniki, Macedonia, Greece
| | - Sang-We Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
| | | | - Giulia Pasello
- Dipartimento di Scienze Chirurgiche, Oncologichee Gastroenterologiche (DiSCOG) dell’Università di Padova, Oncologia 2, Istituto Oncologico Veneto IRCCS, 64 Padova, Italy
| | - Michael Duruisseaux
- Department of Medical Oncology, CHU de Lyon - Hôpital Lyon Sud, 69495 Lyon, France
| | - Spyridon Gennatas
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 7EH, United Kingdom
| | - Anastasios Dimou
- Department of Oncology, Mayo Clinic, Rochester, MN 55905, United States
| | - Bhakti Mehta
- Amgen Inc., Thousand Oaks, CA 91320, United States
| | | | | | | | | | - Yang Wang
- Amgen Inc., Thousand Oaks, CA 91320, United States
| | - Adrianus Johannes de Langen
- Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Thoracic Oncology, 1066 CX Amsterdam, The Netherlands
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Pei Z, Xiao N, Yang P. Cost-effectiveness analysis of Tumor Treating Fields treatment in Chinese patients with metastatic non-small cell lung cancer. Front Public Health 2024; 12:1276049. [PMID: 39502829 PMCID: PMC11534589 DOI: 10.3389/fpubh.2024.1276049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 10/07/2024] [Indexed: 11/08/2024] Open
Abstract
Background The LUNAR trial demonstrated the significant efficacy and safety of Tumor Treating Fields (TTFields) plus standard-of-care (SOC) [immune checkpoint inhibitor (ICI) and docetaxel (DTX)] for patients with previously treated metastatic non-small cell lung cancer (mNSCLC). However, it remains uncertain as to whether the high costs are justified by the corresponding survival benefits. Here, the cost-effectiveness of using TTFields plus SOC for treating mNSCLC was evaluated from the perspective of the Chinese healthcare system. Methods A Markov model with a 15-year time horizon was established and used to comparedeveloped to enable the simulation of treatment-associated costs and patient outcomes when comparing TTFields plus SOC to SOC alone. Primary outcomes for these analyses included total costs, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER) values. The impact of paramere uncertainty on model outcomes was evaluated through sensitivity analyses. Additional subgroup and scenario analyses were also performed to extend these results. Results While TTFields plus SOC exhibited a $74,688 increase in total costs relative to SOC ($96,092 vs. $21,404), it was associated with 0.38 additional QALYs (1.08 vs. 0.82 QALYs) for an ICER of $284,490/QALY. This value exceeded the $35,983/QALY willingness-to-pay (WTP) threshold selected for these analyses by a wide margin. Relative to ICI and DTX treatment, the incremental costs of TTFields plus ICI and TTFields plus DTX were $78,115 and $71,307, respectively, with corresponding gains of 0.42 and 0.13 QALYs, yielding ICERs of $187,434/QALY, and $546,386/QALY. The parameter that most strongly impacted the results of these analyses was the cost of TTFields. Conclusion The results indicated that given current treatment costs, TTFields plus SOC was insufficiently cost-effective in treating patients with mNSCLC in China, although TTFields plus ICI yields substantial health benefits.
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Affiliation(s)
- Zhengda Pei
- Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, China
- Hunan Cancer Hospital, The Affiliate Hospital of Xiangya Medical School, Central South University, Changsha, China
| | - Ningping Xiao
- Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, China
- Hunan Cancer Hospital, The Affiliate Hospital of Xiangya Medical School, Central South University, Changsha, China
| | - Pei Yang
- Graduate Collaborative Training Base of Hunan Cancer Hospital, Hengyang Medical School, University of South China, Hengyang, China
- Hunan Cancer Hospital, The Affiliate Hospital of Xiangya Medical School, Central South University, Changsha, China
- Key Laboratory of Translational Radiation Oncology, Changsha, China
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Shi Z, Zeng X, Sun W, Xu M, Shao K, Wei J, Xu C, Song Z. Efficacy and Safety of First-Line Platinum-Based Doublet Chemotherapy in Advanced Primary Pulmonary Salivary Gland Tumors (PSGTs). Cancer Invest 2024; 42:793-800. [PMID: 39283148 DOI: 10.1080/07357907.2024.2399046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 08/25/2024] [Indexed: 11/01/2024]
Abstract
Primary pulmonary salivary gland tumors (PSGT) constitute a rare subtype of non-small cell lung cancer (NSCLC). Currently, no established treatment guidelines exist for advanced PSGT. The efficacy of platinum-based chemotherapy for PSGT within the context of NSCLC remains uncertain. Therefore, we retrospectively collected 37 PSGT patients who underwent first-line platinum-based chemotherapy from 2010 to 2023. Survival analysis, employing the Kaplan-Meier method, and group comparisons via the log rank test were conducted. Our results show that first-line platinum-based chemotherapy demonstrates favorable efficacy and manageable safety in advanced PSGT, with the combination of Paclitaxel + Platinum emerging as a preferred option.
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Affiliation(s)
- Zheng Shi
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
- Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Xiaohong Zeng
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
- Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Wei Sun
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
- Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Manyi Xu
- Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Keda Shao
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
- Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Jingwen Wei
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
- Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Chunwei Xu
- Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Zhengbo Song
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
- Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
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Tafenzi HA, Choulli F, Haag EK, Baladi A, Essaadi I, Belbaraka R. Real world results of locally advanced and metastatic lung cancer patients treated with platinum doublet chemotherapy in first line: Moroccan cohort. Transl Oncol 2024; 47:102015. [PMID: 38981247 PMCID: PMC11292509 DOI: 10.1016/j.tranon.2024.102015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 04/26/2024] [Accepted: 05/27/2024] [Indexed: 07/11/2024] Open
Abstract
BACKGROUND Doublet platin-chemotherapy was the old standard treatment for different histology types of advanced and metastatic lung cancer (LC) and is still an option for patients who are not eligible for immune checkpoint inhibitors. However, in low- and middle-income countries, chemotherapy, either in monotherapy or in combination with platinum, is still the only accessible option in public institutions. The efficacy of different platin-based chemotherapy in patients with LC who are treatment-naïve is unknown. METHODS In this retrospective study, we selected patients with advanced and metastatic (IIIB-IVB) non-squamous non-small cell LC (NSCLC), squamous NSCLC, and lung neuroendocrine tumours (small cell LC (SCLC), large cell neuroendocrine, and atypical carcinoid) aged beyond 18 years who received first-line chemotherapy (docetaxel, gemcitabine, etoposide, paclitaxel, pemetrexed, and vinorelbine) combined with platinum between January 1, 2013, and December 31, 2022. Within the population with non-squamous NSCLC, squamous NSCLC, and neuroendocrine tumours, progression-free survival (PFS) and overall survival (OS) were the primary assessed endpoints. Hematologic safety was the secondary endpoint. RESULTS Overall, 611 patients were included. In the group of patients with non-squamous NSCLC (n = 390), there was no statistical difference between subgroups of patients who received first-line platin-chemotherapy. The median PFS was 182 (95 % confidence interval [CI], 167-208) days (hazard ratio for progression: NR [Not Reached]; p = 0.37), and the median OS was 446 (95 % CI, 405-559) days (hazard ratio for death: 1.31; 95 % CI, 0.94 - 1.82; p = 0.1). In the group of patients with squamous NSCLC (n = 149), we note the absence of statistical significance between subgroups of patients who received platin-based chemotherapy. The median PFS was 195 (95 % CI, 142-238; hazard ratio for progression: 1.21, 95 % CI, 0.29-5.02; p = 0.27), while the median OS was 428 (95 % CI, 324-940) days (hazard ratio for death: 1.76; 95 % CI, 0.93 to 3.3; p = 0.32). The absence of significance has been noticed in the neuroendocrine subgroup of patients who received first etoposide-platinum, vinorelbine-platinum, or paclitaxel-platinum (n = 72). The median PFS was 216 (95 % CI, 193-277) days; hazard ratio for progression: 1.74, 95 % CI, 0.41-7.27; p = 0.69, while the median OS was 273 (95 % CI, 241-459) days (hazard ratio for death: 2.95; 95 % CI, 0.4-21.7; p = 0.51). Grade 3-4 neutropenia grade was the predominant adverse event associated with chemotherapy in almost 11 % of patients. CONCLUSION Moving forward, treatment strategies must be refined for patients, with an emphasis on increasing the number of patients who can benefit from emergent approaches in order to guarantee a wider, deeper, and longer-lasting outcome.
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Affiliation(s)
- Hassan Abdelilah Tafenzi
- Medical Oncology Department, Mohammed VI University Hospital of Marrakech, Morocco; Biosciences and Health Laboratory, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech, Morocco.
| | - Farah Choulli
- Medical Oncology Department, Mohammed VI University Hospital of Marrakech, Morocco; Biosciences and Health Laboratory, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech, Morocco
| | - Edwin Kelly Haag
- Medical Oncology Department, Mohammed VI University Hospital of Marrakech, Morocco
| | - Anass Baladi
- Medical Oncology Department, Mohammed VI University Hospital of Marrakech, Morocco
| | - Ismail Essaadi
- Biosciences and Health Laboratory, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech, Morocco; Medical Oncology Department, Avicenna Military Hospital of Marrakech, Morocco
| | - Rhizlane Belbaraka
- Medical Oncology Department, Mohammed VI University Hospital of Marrakech, Morocco; Biosciences and Health Laboratory, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech, Morocco
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Liu K, Zhu Y, Zhu H, Zeng M. Combination tumor-treating fields treatment for patients with metastatic non-small cell lung cancer: A cost-effectiveness analysis. Cancer Med 2024; 13:e7070. [PMID: 38468503 DOI: 10.1002/cam4.7070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 02/12/2024] [Accepted: 02/20/2024] [Indexed: 03/13/2024] Open
Abstract
BACKGROUND Tumor-treating field (TTFields) was a novel antitumor therapy that provided significant survival for previously treated metastatic non-small cell lung cancer (mNSCLC). The consistency of the cost of the new treatment regimen with its efficacy was the main objective of the study. METHODS The primary parameters, derived from the Phase 3 LUNAR study, were collected to evaluate the cost and efficacy of TTFields plus standard-of-care (SOC) (immune checkpoint inhibitors [ICIs] and docetaxel [DTX]) or SOC in patients with mNSCLC by establishing a three-state Markov model over a 15-year time horizon. Primary outcome measures for this study included costs, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed. RESULTS The total costs of TTFields plus SOC, TTFields plus ICI, and TTFields plus DTX were $319,358, $338,688, and $298,477, generating 1.23 QALYs, 1.58 QALYs, and 0.89 QALYs, respectively. The ICERs of TTFields plus SOC versus SOC, TTFields plus ICI versus ICI, and TTFields plus DTX versus DTX were $613,379/QALY, $387,542/QALY, and $1,359,559/QALY, respectively. At willingness-to-pay (WTP) thresholds of $150,000/QALY, the probability of combination TTFields being cost-effective was 0%. In addition, TTFields plus SOC exhibited similar efficacy (1.12 QALYs and 1.14 QALYs) and costs ($309,822 and $312,531) in the treatment of squamous cell carcinoma (SCC) and non-squamous cell carcinoma (NSCC) populations. CONCLUSIONS In the United States, TTFields plus SOC as second-line treatment was not a more cost-effective strategy for patients with mNSCLC. Of the analyzed regimens, TTFields plus ICI was associated with most significant health benefits.
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Affiliation(s)
- Kun Liu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Youwen Zhu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Hong Zhu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Manting Zeng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
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Qin K, Wang K, Li S, Hong L, Padmakumar P, Waree R, Hubert SM, Le X, Vokes N, Rai K, Vaporciyan A, Gibbons DL, Heymach JV, Lee JJ, Woodman SE, Chung C, Jaffray DA, Altan M, Lou Y, Zhang J. Clinical Benefit from Docetaxel +/- Ramucirumab Is Not Associated with Mutation Status in Metastatic Non-Small-Cell Lung Cancer Patients Who Progressed on Platinum Doublets and Immunotherapy. Cancers (Basel) 2024; 16:935. [PMID: 38473297 PMCID: PMC10931294 DOI: 10.3390/cancers16050935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 02/07/2024] [Accepted: 02/21/2024] [Indexed: 03/14/2024] Open
Abstract
Docetaxel +/- ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/- ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/- ramucirumab n=381; platinum/taxane-based regimens n=73). Progression-free survival (PFS) and overall survival (OS) were compared among different subpopulations with different cancer gene mutations and between patients who received docetaxel +/- ramucirumab versus platinum/taxane-based regimens. Among patients who received docetaxel +/- ramucirumab, the top mutated cancer genes included TP53 (n=167), KRAS (n=127), EGFR (n=65), STK11 (n=32), ERBB2 (HER2) (n=26), etc. None of these cancer gene mutations or PD-L1 expression was associated with PFS or OS. Platinum/taxane-based regimens were associated with a significantly longer mQS (13.00 m, 95% Cl: 11.20-14.80 m versus 8.40 m, 95% Cl: 7.12-9.68 m, LogRank P=0.019) than docetaxel +/- ramcirumab. Key prognostic factors including age, histology, and performance status were not different between these two groups. In conclusion, in patients with metastatic NSCLC who have progressed on platinum doublets and ICIs, the clinical benefit from docetaxel +/- ramucirumab is not associated with the cancer gene mutation status. Platinum/taxane-based regimens may offer a superior clinical benefit over docetaxel +/- ramucirumab in this patient population.
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Affiliation(s)
- Kang Qin
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (K.Q.); (L.H.); (R.W.); (S.M.H.); (X.L.); (N.V.); (D.L.G.); (J.V.H.); (M.A.)
| | - Kaiwen Wang
- Division of Pharmacy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Shenduo Li
- Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL 32224, USA;
| | - Lingzhi Hong
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (K.Q.); (L.H.); (R.W.); (S.M.H.); (X.L.); (N.V.); (D.L.G.); (J.V.H.); (M.A.)
- Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Priyadharshini Padmakumar
- Department of Enterprise Data Engineering and Analytics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Rinsurongkawong Waree
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (K.Q.); (L.H.); (R.W.); (S.M.H.); (X.L.); (N.V.); (D.L.G.); (J.V.H.); (M.A.)
| | - Shawna M. Hubert
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (K.Q.); (L.H.); (R.W.); (S.M.H.); (X.L.); (N.V.); (D.L.G.); (J.V.H.); (M.A.)
| | - Xiuning Le
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (K.Q.); (L.H.); (R.W.); (S.M.H.); (X.L.); (N.V.); (D.L.G.); (J.V.H.); (M.A.)
| | - Natalie Vokes
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (K.Q.); (L.H.); (R.W.); (S.M.H.); (X.L.); (N.V.); (D.L.G.); (J.V.H.); (M.A.)
| | - Kunal Rai
- Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Ara Vaporciyan
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Don L. Gibbons
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (K.Q.); (L.H.); (R.W.); (S.M.H.); (X.L.); (N.V.); (D.L.G.); (J.V.H.); (M.A.)
| | - John V. Heymach
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (K.Q.); (L.H.); (R.W.); (S.M.H.); (X.L.); (N.V.); (D.L.G.); (J.V.H.); (M.A.)
| | - J. Jack Lee
- Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Scott E. Woodman
- Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Caroline Chung
- Department of Radiation Oncology and Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
- Institute for Data Science in Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - David A. Jaffray
- Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
- Institute for Data Science in Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Mehmet Altan
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (K.Q.); (L.H.); (R.W.); (S.M.H.); (X.L.); (N.V.); (D.L.G.); (J.V.H.); (M.A.)
| | - Yanyan Lou
- Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL 32224, USA;
| | - Jianjun Zhang
- Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (K.Q.); (L.H.); (R.W.); (S.M.H.); (X.L.); (N.V.); (D.L.G.); (J.V.H.); (M.A.)
- Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
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Gijtenbeek RG, de Jong K, Venmans BJ, van Vollenhoven FH, Ten Brinke A, Van der Wekken AJ, van Geffen WH. Best first-line therapy for people with advanced non-small cell lung cancer, performance status 2 without a targetable mutation or with an unknown mutation status. Cochrane Database Syst Rev 2023; 7:CD013382. [PMID: 37419867 PMCID: PMC10327404 DOI: 10.1002/14651858.cd013382.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/09/2023]
Abstract
BACKGROUND Most people who are newly diagnosed with non-small cell lung cancer (NSCLC) have advanced disease. For these people, survival is determined by various patient- and tumor-related factors, of which the performance status (PS) is the most important prognostic factor. People with PS 0 or 1 are usually treated with systemic therapies, whereas people with PS 3 or 4 most often receive supportive care. However, treatment for people with PS 2 without a targetable mutation remains unclear. Historically, people with a PS 2 cancer are frequently excluded from (important) clinical trials because of poorer outcomes and increased toxicity. We aim to address this knowledge gap, as this group of people represents a significant proportion (20% to 30%) of the total population with newly diagnosed lung cancer. OBJECTIVES To identify the best first-line therapy for advanced lung cancer in people with performance status 2 without a targetable mutation or with an unknown mutation status. SEARCH METHODS We used standard, extensive Cochrane search methods. The latest search date was 17 June 2022. SELECTION CRITERIA We included randomized controlled trials (RCTs) that compared different chemotherapy (with or without angiogenesis inhibitor) or immunotherapy regimens, specifically designed for people with PS 2 only or studies including a subgroup of these people. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were 1. overall survival (OS), 2. health-related quality of life (HRQoL), and 3. toxicity/adverse events. Our secondary outcomes were 4. tumor response rate, 5. progression-free survival, and 6. survival rates at six and 12 months' treatment. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS We included 22 trials in this review and identified one ongoing trial. Twenty studies compared chemotherapy with different regimens, of which 11 compared non-platinum therapy (monotherapy or doublet) versus platinum doublet. We found no studies comparing best supportive care with chemotherapy and only two abstracts analyzing chemotherapy versus immunotherapy. We found that platinum doublet therapy showed superior OS compared to non-platinum therapy (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.57 to 0.78; 7 trials, 697 participants; moderate-certainty evidence). There were no differences in six-month survival rates (risk ratio [RR] 1.00, 95% CI 0.72 to 1.41; 6 trials, 632 participants; moderate-certainty evidence), whereas 12-month survival rates were improved for treatment with platinum doublet therapy (RR 0.92, 95% CI 0.87 to 0.97; 11 trials, 1567 participants; moderate-certainty evidence). PFS and tumor response rate were also better for people treated with platinum doublet therapy, with moderate-certainty evidence (PFS: HR 0.57, 95% CI 0.42 to 0.77; 5 trials, 487 participants; tumor response rate: RR 2.25, 95% CI 1.67 to 3.05; 9 trials, 964 participants). When analyzing toxicity rates, we found that platinum doublet therapy increased grade 3 to 5 hematologic toxicities, all with low-certainty evidence (anemia: RR 1.98, 95% CI 1.00 to 3.92; neutropenia: RR 2.75, 95% CI 1.30 to 5.82; thrombocytopenia: RR 3.96, 95% CI 1.73 to 9.06; all 8 trials, 935 participants). Only four trials reported HRQoL data; however, the methodology was different per trial and we were unable to perform a meta-analysis. Although evidence is limited, there were no differences in 12-month survival rates or tumor response rates between carboplatin and cisplatin regimens. With an indirect comparison, carboplatin seemed to have better 12-month survival rates than cisplatin compared to non-platinum therapy. The assessment of the efficacy of immunotherapy in people with PS 2 was limited. There might be a place for single-agent immunotherapy, but the data provided by the included studies did not encourage the use of double-agent immunotherapy. AUTHORS' CONCLUSIONS This review showed that as a first-line treatment for people with PS 2 with advanced NSCLC, platinum doublet therapy seems to be preferred over non-platinum therapy, with a higher response rate, PFS, and OS. Although the risk for grade 3 to 5 hematologic toxicity is higher, these events are often relatively mild and easy to treat. Since trials using checkpoint inhibitors in people with PS 2 are scarce, we identified an important knowledge gap regarding their role in people with advanced NSCLC and PS 2.
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Affiliation(s)
- Rolof Gp Gijtenbeek
- Department of Pulmonary Diseases, Medical Center Leeuwarden, Leeuwarden, Netherlands
| | - Kim de Jong
- Department of Epidemiology, Medical Center Leeuwarden, Leeuwarden, Netherlands
| | - Ben Jw Venmans
- Department of Pulmonary Diseases, Medical Center Leeuwarden, Leeuwarden, Netherlands
| | | | - Anneke Ten Brinke
- Department of Pulmonary Diseases, Medical Center Leeuwarden, Leeuwarden, Netherlands
| | - Anthonie J Van der Wekken
- Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
| | - Wouter H van Geffen
- Department of Pulmonary Diseases, Medical Center Leeuwarden, Leeuwarden, Netherlands
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Sharma K, Mayer T, Li S, Qureshi S, Farooq F, Vuylsteke P, Ralefala T, Marlink R. Advancing oncology drug therapies for sub-Saharan Africa. PLOS GLOBAL PUBLIC HEALTH 2023; 3:e0001653. [PMID: 37368872 DOI: 10.1371/journal.pgph.0001653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/29/2023]
Abstract
Cancer incidence is rising across sub-Saharan Africa (SSA), and is often characterized by late-stage presentation, early age of onset and poor survival. While a number of oncology drugs are now improving the length and quality of life for cancer patients in high-income countries, significant disparities in access to a range of oncology therapeutics exist for SSA. A number of challenges to drug access such as drug costs, lack of infrastructure and trained personnel must be urgently addressed to advance oncology therapies for SSA. We present a review of selected oncology drug therapies that are likely to benefit cancer patients with a focus on common malignancies in SSA. We collate available data from seminal clinical trials in high-income countries to highlight the potential for these therapeutics to improve cancer outcomes. In addition, we discuss the need to ensure access to drugs within the WHO Model List of Essential Medicines and highlight therapeutics that require consideration. Available and active oncology clinical trials in the region is tabulated, demonstrating the significant gaps in access to oncology drug trials across much of the region. We issue an urgent call to action to address drug access due to the predicted rise in cancer burden in the region in coming years.
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Affiliation(s)
- Kirthana Sharma
- Rutgers Global Health Institute, New Brunswick, New Jersey, United States of America
- Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America
| | - Tina Mayer
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States of America
| | - Sharon Li
- Rutgers Cancer Institute at University Hospital, New Jersey Medical School, Newark, New Jersey, United States of America
| | - Sadaf Qureshi
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States of America
| | - Faheem Farooq
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States of America
| | - Peter Vuylsteke
- Department of Internal Medicine, University of Botswana, Gaborone, Botswana
| | - Tlotlo Ralefala
- Department of Oncology, Princess Marina Hospital, Gaborone, Botswana
| | - Richard Marlink
- Rutgers Global Health Institute, New Brunswick, New Jersey, United States of America
- Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America
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Tsai LL, Phillips WW, Hung YP, Dominas C, Deans K, Ahn S, Ferland B, Weiss K, Lanuti M, Auchincloss H, Schumacher L, Jonas O, Colson YL. First-in-Human Intrathoracic Implantation of Multidrug-Eluting Microdevices for In Situ Chemotherapeutic Sensitivity Testing as Proof of Concept in Nonsmall Cell Lung Cancer. Ann Surg 2023; 277:e1143-e1149. [PMID: 35129472 DOI: 10.1097/sla.0000000000005385] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To evaluate the safety and feasibility of implantation and retrieval of a novel implantable microdevice (IMD) in NSCLC patients undergoing operative resection. BACKGROUND Adjuvant therapy has limited impact on postsurgical outcomes in NSCLC due to the inability to predict optimal treatment regimens. METHODS An IMD measuring 6.5 mm by 0.7 mm, containing micro-reservoirs allowing for high-throughput localized drug delivery, was developed and loaded with 12 chemotherapeutic agents. Five patients with peripheral lung lesions larger than 1.0 cm were enrolled in this phase 1 clinical study. IMDs were inserted into tumors intraoperatively under direct vision, removed with the resected specimen, and retrieved in pathology. Surrounding tissues were sectioned, stained, and analyzed for tissue drug response to the IMD-delivered microdoses of these agents by a variety of pharmacodynamic markers. RESULTS A total of 14 IMDs were implanted intraoperatively with 13 (93%) successfully retrieved. After technique refinement, IMDs were reliably inserted and retrieved in open, Video-Assisted Thoracoscopic Surgery, and robotic cases. No severe adverse reactions were observed. The one retained IMD has remained in place without movement or any adverse effects. Analysis of patient blood revealed no detection of chemotherapeutic agents. We observed differential sensitivities of patient tumors to the drugs on the IMD. CONCLUSIONS A multi-drug IMD can be safely inserted and retrieved into lung tumors during a variety of surgical approaches. Future studies will encompass preoperative placement to better examine specific tumor responsiveness to therapeutic agents, allowing clinicians to tailor treatment regimens to the microenvironment of each patient.
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Affiliation(s)
- Lillian L Tsai
- Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - William W Phillips
- Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Yin P Hung
- Department of Pathology, Massachusetts General Hospital, Boston, MA
| | - Christine Dominas
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA
| | - Kyle Deans
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA
| | - Sebastian Ahn
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA
| | - Benjamin Ferland
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA
| | - Kathleen Weiss
- Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Michael Lanuti
- Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Hugh Auchincloss
- Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Lana Schumacher
- Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Oliver Jonas
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA
| | - Yolonda L Colson
- Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA
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11
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Matsuda A, Yamaoka K, Kunitoh H, Seto T, Tsuboi M, Ohira T, Maruyama R, Okamoto H, Kubota K. Quality of life with docetaxel plus cisplatin versus paclitaxel plus carboplatin in patients with completely resected non-small cell lung cancer: quality of life analysis of TORG 0503. Qual Life Res 2023:10.1007/s11136-023-03424-y. [PMID: 37126140 DOI: 10.1007/s11136-023-03424-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/12/2023] [Indexed: 05/02/2023]
Abstract
PURPOSE The TORG0503 study was undertaken to select a preferred platinum-based third-generation regimen for patients with completely resected non-small cell lung cancer (NSCLC). This study aimed to describe the quality of life (QOL) analysis of that study. METHODS Patients with completely resected NSCLC were randomized to receive three cycles of docetaxel plus cisplatin (DC) or paclitaxel plus carboplatin (PC) on day 1 every 3 weeks. QOL was assessed at three time points (baseline, after two cycles, and after three cycles) using the Functional Assessment of Cancer Therapy-taxane (FACT-Taxane). The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression analysis that was adjusted for the baseline score in the FACT-Taxane total score and each subscale to evaluate treatment (PC vs. DC) effectiveness. RESULTS QOL data from 104 patients (DC, n = 56 patients; PC, n = 48) were analyzed. In the FACT-Taxane total score, the baseline-adjusted OR (95% CI) of not worse QOL for the DC group was 3.3 (1.4-8.3) compared with the PC group. In the taxane subscale, the baseline-adjusted OR (95% CI) was 6.2 (2.6-16.0). CONCLUSION Total QOL was maintained better in the DC group than in the PC group, especially the taxane subscale that consists of neurotoxicity and taxane components in spite of no treatment-related death in both arms between DC and PC. We might recommend DC as the control regimen for the next clinical trial from the viewpoint of QOL, similar to the primary outcomes in TORG0503.
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Affiliation(s)
- Ayako Matsuda
- Center for Health Informatics policy, National Institute of Public Health, 2-3-6 Minami, Wako-Shi, Saitama, 351-0197, Japan.
| | - Kazue Yamaoka
- Teikyo University Graduate School of Public Health, Tokyo, Japan
| | - Hideo Kunitoh
- Department of Internal Medicine, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Takashi Seto
- Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan
| | - Masahiro Tsuboi
- Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Tatsuo Ohira
- Department of Surgery, Tokyo Medical University, Tokyo, Japan
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Chakrabarty N, Mahajan A, Patil V, Noronha V, Prabhash K. Imaging of brain metastasis in non-small-cell lung cancer: indications, protocols, diagnosis, post-therapy imaging, and implications regarding management. Clin Radiol 2023; 78:175-186. [PMID: 36503631 DOI: 10.1016/j.crad.2022.09.134] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 09/09/2022] [Accepted: 09/29/2022] [Indexed: 12/14/2022]
Abstract
Increased survival (due to the use of targeted therapies based on genomic profiling) has resulted in the increased incidence of brain metastasis during the course of disease, and thus, made it essential to have proper imaging guidelines in place for brain metastasis from non-small-cell lung cancer (NSCLC). Brain parenchymal metastases can have varied imaging appearances, and it is pertinent to be aware of the various molecular risk factors for brain metastasis from NSCLC along with their suggestive imaging appearances, so as to identify them early. Leptomeningeal metastasis requires additional imaging of the spine and an early cerebrospinal fluid (CSF) analysis. Differentiation of post-therapy change from recurrence on imaging has a bearing on the management, hence the need for its awareness. This article will provide in-depth literature review of the epidemiology, aetiopathogenesis, screening, detection, diagnosis, post-therapy imaging, and implications regarding the management of brain metastasis from NSCLC. In addition, we will also briefly highlight the role of artificial intelligence (AI) in brain metastasis screening.
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Affiliation(s)
- N Chakrabarty
- Department of Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, 400 012, Maharashtra, India
| | - A Mahajan
- Department of Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, 400 012, Maharashtra, India.
| | - V Patil
- Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, 400 012, Maharashtra, India
| | - V Noronha
- Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, 400 012, Maharashtra, India
| | - K Prabhash
- Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, 400 012, Maharashtra, India
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The predictive model for risk of chemotherapy-induced thrombocytopenia based on antineoplastic drugs for solid tumors in eastern China. Sci Rep 2023; 13:3185. [PMID: 36823199 PMCID: PMC9950128 DOI: 10.1038/s41598-023-27824-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 01/09/2023] [Indexed: 02/25/2023] Open
Abstract
Chemotherapy-related thrombocytopenia (CIT) is a significant adverse event during chemotherapy, which can lead to reduced relative dose intensity, increased risk of serious bleeding and additional medical expenditure. Herein, we aimed to develop and validate a predictive nomogram model for prediction of CIT in patients with solid tumor. From Jun 1, 2018 to Sep 9, 2021, a total of 1541 patients who received 5750 cycles of chemotherapy were retrospectively enrolled. Cox regression analysis was performed to identify predictive factors to establish the nomogram model for CIT. The incidence of chemotherapy-induced thrombocytopenia was 21.03% for patient-based and 10.26% for cycles of chemotherapy. The top five solid tumors with CIT are cervix, gastric, bladder, biliary systemic, and ovarian. The incidence of chemotherapy dose delays in any cycle because of CIT was 5.39%. Multivariate analysis showed that tumor site, treatment line, AST, oxaliplatin, and capecitabine were significantly associated with CIT. Moreover, we established a nomogram model for CIT probability prediction, and the model was well calibrated (Hosme-Lemeshow P = 0.230) and the area under the receiver operating characteristic curve was 0.844 (Sensitivity was 0.625, Specificity was 0.901). We developed a predictive model for chemotherapy-induced thrombocytopenia based on readily available and easily assessable clinical characteristics. The predictive model based on clinical and laboratory indices represents a promising tool in the prediction of CIT, which might complement the clinical management of thrombocytopenia.
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14
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Zarkavelis G, Amylidi AL, Verbaanderd C, Cherny NI, Metaxas Y, de Vries EGE, Zygoura P, Amaral T, Jordan K, Strijbos M, Dafni U, Latino N, Galotti M, Lordick F, Giuliani R, Pignatti F, Pentheroudakis G. Off-label despite high-level evidence: a clinical practice review of commonly used off-patent cancer medicines. ESMO Open 2023; 8:100604. [PMID: 36870739 PMCID: PMC10024100 DOI: 10.1016/j.esmoop.2022.100604] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 09/10/2022] [Indexed: 11/16/2022] Open
Abstract
INTRODUCTION Off-label use of medicines is generally discouraged. However, several off-patent, low-cost cancer medicines remain off-label for indications in which they are commonly used in daily practice, supported by high-level evidence based on results of phase III clinical trials. This discrepancy may generate prescription and reimbursement obstacles as well as impaired access to established therapies. METHODS A list of cancer medicines that remain off-label in specific indications despite the presence of high-level evidence was generated and subjected to European Society for Medical Oncology (ESMO) expert peer review to assess for accountability of reasonableness. These medicines were then surveyed on approval procedures and workflow impact. The most illustrative examples of these medicines were reviewed by experts from the European Medicines Agency to ascertain the apparent robustness of the supporting phase III trial evidence from a regulatory perspective. RESULTS A total of 47 ESMO experts reviewed 17 cancer medicines commonly used off-label in six disease groups. Overall, high levels of agreement were recorded on the off-label status and the high quality of data supporting the efficacy in the off-label indications, often achieving high ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scores. When prescribing these medicines, 51% of the reviewers had to implement a time-consuming process associated with additional workload, in the presence of litigation risks and patient anxiety. Finally, the informal regulatory expert review identified only 2 out of 18 (11%) studies with significant limitations that would be difficult to overcome in the context of a potential marketing authorisation application without additional studies. CONCLUSIONS We highlight the common use of off-patent essential cancer medicines in indications that remain off-label despite solid supporting data as well as generate evidence on the adverse impact on patient access and clinic workflows. In the current regulatory framework, incentives to promote the extension of indications of off-patent cancer medicines are needed for all stakeholders.
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Affiliation(s)
- G Zarkavelis
- University of Ioannina-Department of Medical Oncology, Ioannina, Greece
| | - A L Amylidi
- University of Ioannina-Department of Medical Oncology, Ioannina, Greece
| | - C Verbaanderd
- European Medicines Agency, Amsterdam, the Netherlands
| | - N I Cherny
- Cancer Pain and Palliative Medicine Service, Department of Medical Oncology, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Y Metaxas
- Kantonsspital Münsterlingen, Münsterlingen, Switzerland
| | - E G E de Vries
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - P Zygoura
- Frontier Science Foundation-Hellas, Athens, Greece
| | - T Amaral
- Skin Cancer Center, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany
| | - K Jordan
- Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany; Department of Hematology, Oncology and Palliative Medicine, Ernst von Bergmann Hospital Potsdam, Potsdam, Germany
| | - M Strijbos
- GZA Ziekenhuizen Campus Sint-Augustinus, Antwerp, Belgium
| | - U Dafni
- Frontier Science Foundation-Hellas, Athens, Greece; Laboratory of Biostatistics, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece
| | - N Latino
- ESMO Head Office, Lugano, Switzerland
| | - M Galotti
- ESMO Head Office, Lugano, Switzerland
| | - F Lordick
- Department of Oncology, Gastroenterology, Hepatology, Pulmonology and Infectious Diseases, University Cancer Center Leipzig (UCCL), Leipzig University Medical Center, Leipzig, Germany
| | - R Giuliani
- The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK
| | - F Pignatti
- European Medicines Agency, Amsterdam, the Netherlands
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Laktionov KK, Artamonova EV, Borisova TN, Breder VV, Bychkov IM, Vladimirova LI, Volkov NM, Ergnian SM, Zhabina AS, Kononets PV, Kuzminov AE, Levchenko EV, Malikhova OA, Marinov DT, Miller SV, Moiseenko FV, Mochal’nikova VV, Novikov SN, Pikin OV, Reutova EV, Rodionov EO, Sakaeva DD, Sarantseva KA, Semenova AI, Smolin AV, Sotnikov VM, Tuzikov SA, Turkin IN, Tyurin IE, Chkhikvadze VD, Kolbanov KI, Chernykh MV, Chernichenko AV, Fedenko AA, Filonenko EV, Nevol’skikh AA, Ivanov SA, Khailova ZV, Gevorkian TG, Butenko AV, Gil’mutdinova IR, Gridneva IV, Eremushkin MA, Zernova MA, Kasparov BS, Kovlen DV, Kondrat’eva KO, Konchugova TV, Korotkova SB, Krutov AA, Obukhova OA, Ponomarenko GN, Semiglazova TI, Stepanova AM, Khulamkhanova MM. Malignant neoplasm of the bronchi and lung: Russian clinical guidelines. JOURNAL OF MODERN ONCOLOGY 2022. [DOI: 10.26442/18151434.2022.3.201848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
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Melichar B. Biomarkers in the management of lung cancer: changing the practice of thoracic oncology. Clin Chem Lab Med 2022; 61:906-920. [PMID: 36384005 DOI: 10.1515/cclm-2022-1108] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 11/02/2022] [Indexed: 11/17/2022]
Abstract
Abstract
Lung cancer currently represents a leading cause of cancer death. Substantial progress achieved in the medical therapy of lung cancer during the last decade has been associated with the advent of targeted therapy, including immunotherapy. The targeted therapy has gradually shifted from drugs suppressing general mechanisms of tumor growth and progression to agents aiming at transforming mechanisms like driver mutations in a particular tumor. Knowledge of the molecular characteristics of a tumor has become an essential component of the more targeted therapeutic approach. There are specific challenges for biomarker determination in lung cancer, in particular a commonly limited size of tumor sample. Liquid biopsy is therefore of particular importance in the management of lung cancer. Laboratory medicine is an indispensable part of multidisciplinary management of lung cancer. Clinical
Chemistry and Laboratory Medicine (CCLM) has played and will continue playing a major role in updating and spreading the knowledge in the field.
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Affiliation(s)
- Bohuslav Melichar
- Department of Oncology , Palacký University Medical School and Teaching Hospital , Olomouc , Czech Republic
- Department of Oncology and Radiotherapy and Fourth Department of Medicine , Charles University Medical School and Teaching Hospital , Hradec Králové , Czech Republic
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Song B, Zhou S, Li C, Zheng H, Zhang X, Jin X, Fu J, Hu H. A Prediction Model for Chemotherapy-Induced Thrombocytopenia Based on Real-World Data and a Close Relationship Between AST/ALT Ratio and Platelet Count in Patients with Solid Tumors. Int J Gen Med 2022; 15:8003-8015. [PMID: 36345528 PMCID: PMC9636883 DOI: 10.2147/ijgm.s383349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 10/10/2022] [Indexed: 01/24/2023] Open
Abstract
OBJECTIVE Chemotherapy-induced thrombocytopenia (CIT) can lead to chemotherapy dose delay or reduction, and even serious bleeding. This study aimed to develop a CIT-predicting model based on the laboratory indices of cancer patients undergoing chemotherapy. MATERIAL AND METHODS From Jun 1, 2017 to Dec 30, 2021, a total of 2043 patients who had received 7676 cycles of chemotherapy were retrospectively enrolled. A logistic regression analysis was performed to identify predictive factors, on the basis of which a nomogram model for predicting CIT was established. A bootstrapping technique was applied for internal validation. A generalized additive mixed model (GAMM) was constructed to analyze the trends in the changes of aspartate aminotransferase (AST), ratio of AST to alanine transaminase (ALT) (AST/ALT ratio), and platelet (PLT) count in patients with solid tumors. P values ≤0.05 were considered statistically significant. RESULTS The patient-based incidence of CIT was 20.51% and the cycle-based incidence was 10.01%. The multivariate analysis showed that AST level, AST/ALT ratio, and total bilirubin (Tbil), white blood cell (WBC), platelet (PLT), hemoglobin (Hb) levels were significantly associated with the risk of CIT. The GAMM analysis showed that PLT level was inversely associated with AST/ALT ratio and AST level, more significantly with AST/ALT ratio. And both exhibited statistically predictive abilities for CIT. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.793, a sensitivity of 0.543 and a specificity of 0.930. CONCLUSION The AST/ALT ratio was inversely associated with the CIT risk in cancer patients. The GAMM model based on laboratory indices presented a high accuracy in predicting the risk of CIT, and a potential to be translated into clinical management.
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Affiliation(s)
- Bingxin Song
- Department of Medical Hematology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang Province, People’s Republic of China
| | - Shishi Zhou
- Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang Province, People’s Republic of China
| | - Chenghui Li
- Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang Province, People’s Republic of China
| | - Hongjuan Zheng
- Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang Province, People’s Republic of China
| | - Xia Zhang
- Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang Province, People’s Republic of China
| | - Xiayun Jin
- Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang Province, People’s Republic of China
| | - Jianfei Fu
- Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang Province, People’s Republic of China,Correspondence: Jianfei Fu, Department of Medical Oncology, Zhejiang University Jinhua Hospital, 351 Mingyue Road, Jinhua, 321000, Zhejiang Province, People’s Republic of China, Fax +86-579-82552856, Email
| | - Huixian Hu
- Department of Medical Hematology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang Province, People’s Republic of China,Huixian Hu, Department of Medical Hematology, Zhejiang University Jinhua Hospital, 351 Mingyue Road, Jinhua, Zhejiang Province, 321000, People’s Republic of China, Fax +86-579-82136611, Email
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cyy-287, a novel pyrimidine-2,4-diamine derivative, inhibits tumor growth of EGFR-driven non-small cell lung cancer via the ERK pathway. Acta Biochim Biophys Sin (Shanghai) 2022; 54:1540-1551. [PMID: 36239356 PMCID: PMC9828441 DOI: 10.3724/abbs.2022139] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
In recent decades, EGFR-targeted tyrosine kinase inhibitors (TKIs) have been proven to be an effective therapy for EGFR-mutant non-small cell lung cancer (NSCLC). However, resistance to EGFR-TKIs limits their clinical application. In the present study, we investigate the antitumor effect and underlying mechanism of a novel pyrimidine-2,4-diamine derivative, cyy-287, in NSCLC. We find that cyy-287 has a high affinity for lung tissue and inhibits the proliferation of NSCLC cells. Interestingly, the significant suppression of migration and induction of apoptosis by cyy-287 are only observed in EGFR-driven but not in EGFR-wild-type (wt) cells. According to the RNA sequencing and KEGG enrichment analysis results, cyy-287 markedly inhibits the MAPK pathway in EGFR-driven PC9 cells, and western blot analysis results further indicate that cyy-287 selectively blocks the ERK pathway in EGFR-driven cells. Meanwhile, apoptosis induced by cyy-287 could be partially reversed by ERK pathway inhibition. Further experiment indicates that cyy-287 inhibits the EGFR pathway in both EGFR-driven and EGFR-overexpressing cells. Interestingly, it only induces apoptosis in EGFR-driven cells, not in EGFR-overexpressing cells. The growth of EGFR-driven cells is suppressed by cyy-287 in vivo, with fewer side effects. Our results suggest that cyy-287 may be a potential therapeutic drug with promising antitumor effects against NSCLC.
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Chen P, Liu Y, Wen Y, Zhou C. Non-small cell lung cancer in China. Cancer Commun (Lond) 2022; 42:937-970. [PMID: 36075878 PMCID: PMC9558689 DOI: 10.1002/cac2.12359] [Citation(s) in RCA: 321] [Impact Index Per Article: 107.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 07/21/2022] [Accepted: 08/24/2022] [Indexed: 04/08/2023] Open
Abstract
In China, lung cancer is a primary cancer type with high incidence and mortality. Risk factors for lung cancer include tobacco use, family history, radiation exposure, and the presence of chronic lung diseases. Most early-stage non-small cell lung cancer (NSCLC) patients miss the optimal timing for treatment due to the lack of clinical presentations. Population-based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in China. The understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC, thus prolonging survival in patients with positive drivers. In the exploration of immune escape mechanisms, programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in China. In the Chinese Society of Clinical Oncology's guidelines for NSCLC, maintenance immunotherapy is recommended for locally advanced NSCLC after chemoradiotherapy. Adjuvant immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable NSCLC. In this review, we summarized recent advances in NSCLC in China in terms of epidemiology, biology, molecular pathology, pathogenesis, screening, diagnosis, targeted therapy, and immunotherapy.
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Affiliation(s)
- Peixin Chen
- School of MedicineTongji UniversityShanghai200092P. R. China
- Department of Medical OncologyShanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghai200433P. R. China
| | - Yunhuan Liu
- Department of Respiratory and Critical Care MedicineHuadong HospitalFudan UniversityShanghai200040P. R. China
| | - Yaokai Wen
- School of MedicineTongji UniversityShanghai200092P. R. China
- Department of Medical OncologyShanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghai200433P. R. China
| | - Caicun Zhou
- School of MedicineTongji UniversityShanghai200092P. R. China
- Department of Medical OncologyShanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghai200433P. R. China
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Does Molecular Profiling of KRAS-Mutant Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Help in Treatment Strategy Planning? Curr Oncol 2022; 29:4779-4790. [PMID: 35877239 PMCID: PMC9315614 DOI: 10.3390/curroncol29070379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 07/04/2022] [Accepted: 07/05/2022] [Indexed: 11/25/2022] Open
Abstract
Background: Several studies suggest that patients with KRAS-mutant NSCLC fail to benefit from standard systemic therapies and do not respond to EGFR inhibitors. Most recently, KRAS 12c data suggest specific treatment for improving ORR and OS. There is a clear need for therapies specifically developed for these patients. Moreover, data that might be suggestive of a response to specific therapies, such as BRCA1, are needed, and two mutations that were studied in other malignancies show more response to PARP inhibitors. Molecular profiling has the potential to identify other potential targets that may provide better treatment and novel targeted therapy for KRAS-mutated NSCLC. Methods: We purified RNA from archived tissues of patients with stage I and II NSCLC with wild-type (wt) and mutant (mt) KRAS tumors; paired normal tissue adjacent to the tumor from 20 and 17 patients, respectively, and assessed, using real-time reverse transcriptase−polymerase chain reaction (RT-PCR), the expression of four genes involved in DNA synthesis and repair, including thymidylate synthase (TS), BRCA1, ECCR1, RAP80, and the proto-oncogene SRC. Additionally, we assessed the expression of PD-L1 in mt KRAS tumors with immunohistochemistry using an antibody against PD-L1. Results: Our results show that in mtKRAS tumors, the level of expression of ERCC1, TS, and SRC was significantly increased in comparison to paired normal lung tissue (p ≤ 0.04). The expression of BRCA1 and RAP80 was similar in both mt KRAS tumors and paired normal tissue. Furthermore, the expression of BRCA1, TS, and SRC was significantly increased in wt KRAS tumors relative to their expression in the normal lung tissue (p < 0.044). The expression of ERCC1 and RAP80 was similar in wt KRAS tumors and paired normal tissue. Interestingly, SRC expression in mtKRAS tumors was decreased in comparison to wt KRAS tumors. Notably, there was an expression of PD-L1 in the tumor and stromal cells in a few (5 out of 20) mtKRAS tumors. Our results suggest that a greater ERCC1 expression in mt KRAS tumors might increase platinum resistance in this group of patients, whereas the greater expression of BRCA1 in wt KRAS tumor might be suggestive of the sensitivity of taxanes. Our data also suggest that the combination of an SRC inhibitor with a TS inhibitor, such as pemetrexed, might improve the outcome of patients with NSCLC and in particular, patients with wt KRAS tumors. PD-L1 expression in tumors, and especially stromal cells, suggests a better outcome. Conclusion: mt KRAS NSCLC patients might benefit from a treatment strategy that targets KRAS in combination with therapeutic agents based on pharmacogenomic markers, such as SRC and BRCA1. mtKRAS tumors are likely to be platinum-, taxane-, and pemetrexed-resistant, as well as having a low level of PD-L1 expression; thus, they are less likely to receive single-agent immunotherapy, such as pembrolizumab, as the first-line therapy. wt KRAS tumors with BRCA1 positivity tend to be sensitive to taxane therapy and, potentially, platinum. Our results suggest the need to develop targeted therapies for KRAS-mutant NSCLC or combine the targeting of oncogenic KRAS in addition to other therapeutic agents specific to the molecular profile of the tumor.
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Liao D, Yu L, Shangguan D, Zhang Y, Xiao B, Liu N, Yang N. Recent Advancements of Monotherapy, Combination, and Sequential Treatment of EGFR/ALK-TKIs and ICIs in Non–Small Cell Lung Cancer. Front Pharmacol 2022; 13:905947. [PMID: 35734411 PMCID: PMC9207473 DOI: 10.3389/fphar.2022.905947] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 05/03/2022] [Indexed: 11/13/2022] Open
Abstract
Lung cancer is the leading cause of cancer-related deaths with high morbidity and mortality. Non–small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 85% of all cases. Fortunately, the development of molecular oncology provides a promising and effective therapeutic strategy for lung cancers, including specific gene mutations/translocations and immune checkpoints, with epidermal growth factor receptor (EGFR) common mutations first and anaplastic lymphoma kinase (ALK) translocations later as the targeted therapy and immune checkpoint inhibitors (ICIs) as immunotherapy. This review summarized the recent therapy advancements of TKIs and ICIs in NSCLC and focused on the clinical effect of combination or sequential treatment so as to provide the effective advice for the treatment of NSCLC.
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Affiliation(s)
- Dehua Liao
- Department of Pharmacy, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Lun Yu
- Department of PET-CT Center, Chenzhou NO. 1 People’s Hospital, Chenzhou, China
| | - Dangang Shangguan
- Department of Pharmacy, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Yongchang Zhang
- Lung Cancer and Gastrointestinal Unit, Department of Medical Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Bowen Xiao
- Department of Pharmacy, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Ni Liu
- Department of Pharmacy, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Nong Yang
- Lung Cancer and Gastrointestinal Unit, Department of Medical Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- *Correspondence: Nong Yang,
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22
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Kubeček O, Paterová P, Novosadová M. Risk Factors for Infections, Antibiotic Therapy, and Its Impact on Cancer Therapy Outcomes for Patients with Solid Tumors. Life (Basel) 2021; 11:1387. [PMID: 34947918 PMCID: PMC8705721 DOI: 10.3390/life11121387] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 12/05/2021] [Accepted: 12/08/2021] [Indexed: 12/12/2022] Open
Abstract
Infections represent a significant cause of morbidity and mortality in cancer patients. Multiple factors related to the patient, tumor, and cancer therapy can affect the risk of infection in patients with solid tumors. A thorough understanding of such factors can aid in the identification of patients with substantial risk of infection, allowing medical practitioners to tailor therapy and apply prophylactic measures to avoid serious complications. The use of novel treatment modalities, including targeted therapy and immunotherapy, brings diagnostic and therapeutic challenges into the management of infections in cancer patients. A growing body of evidence suggests that antibiotic therapy can modulate both toxicity and antitumor response induced by chemotherapy, radiotherapy, and especially immunotherapy. This article provides a comprehensive review of potential risk factors for infections and therapeutic approaches for the most prevalent infections in patients with solid tumors, and discusses the potential effect of antibiotic therapy on toxicity and efficacy of cancer therapy.
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Affiliation(s)
- Ondřej Kubeček
- Department of Oncology and Radiotherapy, Faculty of Medicine and University Hospital in Hradec Králové, Charles University, Sokolská 581, 50005 Hradec Králové, Czech Republic;
| | - Pavla Paterová
- Department of Clinical Microbiology, Faculty of Medicine and University Hospital in Hradec Králové, Charles University, Sokolská 581, 50005 Hradec Králové, Czech Republic
| | - Martina Novosadová
- Department of Clinical Pharmacy, Hospital Pharmacy, University Hospital in Hradec Králové, Sokolská 581, 50005 Hradec Králové, Czech Republic;
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Hao W, Cui Y, Fan Y, Chen M, Yang G, Wang Y, Yang M, Li Z, Gong W, Yang Y, Gao C. Hybrid membrane-coated nanosuspensions for multi-modal anti-glioma therapy via drug and antigen delivery. J Nanobiotechnology 2021; 19:378. [PMID: 34801032 PMCID: PMC8606100 DOI: 10.1186/s12951-021-01110-0] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 11/02/2021] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Glioma is one of the deadliest human cancers. Although many therapeutic strategies for glioma have been explored, these strategies are seldom used in the clinic. The challenges facing the treatment of glioma not only involve the development of chemotherapeutic drugs and immunotherapeutic agents, but also the lack of a powerful platform that could deliver these two moieties to the targeted sites. Herein, we developed chemoimmunotherapy delivery vehicles based on C6 cell membranes and DC membranes to create hybrid membrane-coated DTX nanosuspensions (DNS-[C6&DC]m). RESULTS Results demonstrated successful hybrid membrane fusion and nanosuspension functionalization, and DNS-[C6&DC]m could be used for different modes of anti-glioma therapy. For drug delivery, membrane coating could be applied to target the source cancer cells via a homotypic-targeting mechanism of the C6 cell membrane. For cancer immunotherapy, biomimetic nanosuspension enabled an immune response based on the professional antigen-presenting characteristic of the dendritic cell membrane (DCm), which carry the full array of cancer cell membrane antigens and facilitate the uptake of membrane-bound tumor antigens for efficient presentation and downstream immune n. CONCLUSION DNS-[C6&DC]m is a multifunctional biomimetic nano-drug delivery system with the potential to treat gliomas through tumor-targeted drug delivery combined with immunotherapy, thereby presenting a promising approach that may be utilized for multiple modes of cancer therapy.
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Affiliation(s)
- Wenyan Hao
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People's Republic of China
| | - Yuexin Cui
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People's Republic of China
| | - Yueyue Fan
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People's Republic of China
| | - Mengyu Chen
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People's Republic of China
| | - Guobao Yang
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People's Republic of China
| | - Yuli Wang
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People's Republic of China.
| | - Meiyan Yang
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People's Republic of China
| | - Zhiping Li
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People's Republic of China
| | - Wei Gong
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People's Republic of China
| | - Yang Yang
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People's Republic of China.
| | - Chunsheng Gao
- State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People's Republic of China.
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Kwan TY, Chowdhury EH. Clinical Outcomes of Chemotherapeutic Molecules as Single and Multiple Agents in Advanced Non-Small-Cell Lung Carcinoma (NSCLC) Patients. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:1252. [PMID: 34833470 PMCID: PMC8618045 DOI: 10.3390/medicina57111252] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 11/05/2021] [Accepted: 11/09/2021] [Indexed: 01/11/2023]
Abstract
Background and Objectives: Lung cancer is the second most common cancer in the world. Non-small-cell lung carcinoma (NSCLC) makes up 85% of all lung cancer cases and the majority of patients are diagnosed when the cancer is advanced. Over the years, many anticancer drugs have been designed and introduced into the market to treat patients with advanced NSCLC. This review aims to discuss the comparative therapeutic benefits of conventional chemotherapeutics and other drugs available for treating advanced NSCLC. Materials and Methods: A literature search for first-line treatment of advanced NSCLC was carried out on PubMed and Google Scholar. Objective response rate (ORR) and overall survival were chosen as target endpoints. Results: Monotherapy showed lower treatment endpoints compared to combination therapy. Different combinations of platinum-based doublets demonstrated similar efficacies in treating NSCLC. However, pemetrexed-platinum doublets showed significantly better treatment endpoint in patients with non-squamous NSCLC. Most studies showing the best complete response rate (CRR) utilized epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), while most studies producing the best overall survival included programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in their treatment regimens. Conclusions: The findings of this review indicate that targeted therapy using specific inhibitors is now the most promising first-line anticancer treatment available in the market. However, chemotherapy is still effective in treating advanced NSCLC and is viable as a first-line treatment.
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Affiliation(s)
| | - Ezharul Hoque Chowdhury
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia;
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The genomic landscape of lung adenocarcinoma—insights towards personalized medicine. PROCEEDINGS OF THE INDIAN NATIONAL SCIENCE ACADEMY 2021. [DOI: 10.1007/s43538-021-00054-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Hani U, M. YB, Wahab S, Siddiqua A, Osmani RAM, Rahamathulla M. A Comprehensive Review of Current Perspectives on Novel Drug Delivery Systems and Approaches for Lung Cancer Management. J Pharm Innov 2021. [DOI: 10.1007/s12247-021-09582-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Chen TL, Patel AS, Jain V, Kuppusamy R, Lin YW, Hou MH, Su TL, Lee TC. Discovery of Oral Anticancer 1,2-Bis(hydroxymethyl)benzo[ g]pyrrolo[2,1- a]phthalazine Hybrids That Inhibit Angiogenesis and Induce DNA Cross-Links. J Med Chem 2021; 64:12469-12486. [PMID: 34459195 DOI: 10.1021/acs.jmedchem.0c01733] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Designing hybrid molecules with dual functions is one approach to improve the therapeutic efficacy of combination treatment. We have previously conjugated phthalazine and bis(hydroxymethyl)pyrrole pharmacophores to form hybrids bearing antiangiogenesis and DNA interstrand cross-linking activities. To improve the bioavailability, we adopted a benzology approach to design and synthesize a new series of 1,2-bis(hydroxymethyl)benzo[g]pyrrolo[2,1-a]phthalazines. These new hybrids retained the dual functions and could be formulated into vehicles for intravenous and oral administration. Among them, we demonstrated that compound 19a with dimethylamine at the C6 position markedly suppressed the tumor growth of human small cell lung cancer cell line H526, squamous lung cancer cell line H520, and renal cancer cell line 786-O in nude mice, implying that compound 19a is a broad-spectrum anticancer agent. Our results implicated that the conjugation of antiangiogenic and DNA cross-linking is likely to be a helpful approach to improving the efficacy of combination therapy.
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Affiliation(s)
- Tai-Lin Chen
- Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.,School of Pharmacy, China Medical University, Taichung 40400, Taiwan
| | - Anilkumar S Patel
- Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.,Department of Chemistry, Atmiya University, Rajkot 360005, Gujarat, India
| | - Vicky Jain
- Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.,Department of Chemistry, Marwadi University, Rajkot 360003, Gujarat, India
| | | | - Yi-Wen Lin
- Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
| | - Ming-Hon Hou
- Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung 40227, Taiwan
| | - Tsann-Long Su
- Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
| | - Te-Chang Lee
- Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
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Cui Z, Xu D, Zhang F, Sun J, Song L, Ye W, Zeng J, Zhou M, Ruan Z, Zhang L, Ren R. CD47 blockade enhances therapeutic efficacy of cisplatin against lung carcinoma in a murine model. Exp Cell Res 2021; 405:112677. [PMID: 34111474 DOI: 10.1016/j.yexcr.2021.112677] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 04/28/2021] [Accepted: 05/24/2021] [Indexed: 12/26/2022]
Abstract
Cisplatin (CDDP) is the first generation of platinum-based drug and is widely used to treat many cancers due to its potency. The present study aims to explore the effects of CDDP on lung carcinoma and its relationship with macrophage phagocytosis. In in vitro study, murine and human lung cancer cell lines were applied and treated with CDDP, CD47 antibody (aCD47), or CDDP plus aCD47. In in vivo study, a tumor xenograft animal model was treated with CDDP, aCD47, or CDDP plus aCD47. Real-time PCR was applied to determine the mRNA expressions. Enzyme-linked immunosorbent assay (ELISA), Western blotting, and Immunofluorescent staining were applied to determine the protein expressions. Flow cytometry was applied to analyze cell apoptosis, phagocytosis, and specific cell populations. CDDP enhanced the expressions of CD47 in lung cancer cells. Interestingly, the blockage of CD47 enhanced the macrophages' phagocytic activity on the CDDP-treated tumor cells. The treatment of CDDP and aCD47 exhibited anti-tumor effects and prolonged the LLC tumor-bearing mice survival time. Mechanistic studies revealed that the treatment of CDDP and aCD47 regulated the phagocytic activity of macrophage, percentage of CD8+ T cells, and cytokines (tumor growth factor (TGF)-β, interleukin (IL)12p70, and interferon (IFN)-γ) in the tumor-bearing model. CD47 blockade enhanced therapeutic efficacy of cisplatin against lung carcinoma in vivo and in vitro.
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Affiliation(s)
- Zhilei Cui
- Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China
| | - Dengfei Xu
- Department of Oncology, Henan Key Laboratory for Precision Medicine in Cancer, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, 450003, Henan, China
| | - Fafu Zhang
- Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China
| | - Jinyuan Sun
- Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China
| | - Lin Song
- Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China
| | - Wenjing Ye
- Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China
| | - Junxiang Zeng
- Department of Laboratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China
| | - Min Zhou
- Department of Respiratory Medicine, Jinshan Branch of the Sixth People's Hospital of Shanghai, Shanghai Jiaotong University, China
| | - Zhengshang Ruan
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Linlin Zhang
- Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
| | - Rongrong Ren
- Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
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The real-world efficacy and safety of anlotinib in advanced non-small cell lung cancer. J Cancer Res Clin Oncol 2021; 148:1721-1735. [PMID: 34357411 PMCID: PMC8343360 DOI: 10.1007/s00432-021-03752-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 08/01/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE Anlotinib is an anti-angiogenetic multi-targeted tyrosine kinase inhibitor. This study aimed to evaluate the efficacy and safety of anlotinib in advanced non-small cell lung cancer (aNSCLC) in the real world. METHODS Patients with aNSCLC receiving anlotinib were enrolled in two cohorts (treatment naive and previously treated). The endpoints included progression-free survival (PFS), overall survival (OS) and anlotinib-related adverse events (ar-AEs). RESULTS 203 patients accrued in the study. In the treatment-naïve cohort (n = 80), the PFS was 7.4 (95% confidence interval [CI] 4.1-10.7) and OS was 10.8 (95% CI 5.8-15.8) months of monotherapy group (immature survival for combination group). In previously treated cohort (n = 123), the PFS was 8.0 months (95% CI 6.1-9.9) in the combination group and 4.3 months (95% CI 2.1-6.6) in the monotherapy group (hazard ratio [HR] 0.49; 95% CI 0.29-0.83; p = 0.007), respectively. The OS was 18.5 months (95% CI 10.5-26.6) in the combination group and 7.8 months (95% CI 7.1-8.4) in the monotherapy group (HR 0.38; 95% CI 0.22-0.66; p = 0.001), respectively. The ar-AEs of grade ≥ 3 in the monotherapy and the combination groups were hypertension (9.0 and 8.7%), fatigue (8.1 and 7.6%), hand-foot syndrome (8.1 and 6.5%), diarrhea (5.4 and 8.7%), proteinuria (5.4 and 5.4%), and mucositis oral (6.3 and 8.7%). CONCLUSION In aNSCLC, anlotinib monotherapy has a promising efficacy in the first-line setting. It may be an option for those who are ineligible for chemotherapy; anlotinib combination therapy in a ≥ second-line setting showed manageable toxicities and encouraging efficacy, indicating a good application prospect. TRIAL REGISTRATION This study was retrospectively registered with ISRCTN Registry (ID ISRCTN35543977) on January 26th, 2021 and Chinese Clinical Trial Register (ChiCTR2000032265) on April 4th, 2020.
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Sharma A, Pandey AK, Sharma A, Arora G, Mohan A, Bhalla AS, Gupta L, Biswal SK, Kumar R. Prognostication Based on Texture Analysis of Baseline 18F Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Nonsmall-Cell Lung Carcinoma Patients Who Underwent Platinum-Based Chemotherapy as First-Line Treatment. Indian J Nucl Med 2021; 36:252-260. [PMID: 34658548 PMCID: PMC8481851 DOI: 10.4103/ijnm.ijnm_20_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 06/09/2021] [Accepted: 06/10/2021] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE Our study aims to establish the potential for tumor heterogeneity evaluated using 18F fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) texture analysis in nonsmall-cell lung carcinoma (NSCLC) patients who underwent platinum-based chemotherapy to provide an independent marker for overall survival (OS) of more than 1-year. MATERIALS AND METHODS A total of 42 patients (34 male and 8 female) with biopsy-proven NSCLC and mean age 55.33 ± 10.71 years who underwent a baseline F-18 FDG PET/CT and received platinum-based chemotherapy as first-line treatment were retrospectively included in the study. Ten first order, 21 s order texture parameters and 7 SUV and metabolic tumor volume (MTV) based metabolic parameters were calculated. All these parameters were compared between the two survival groups based on OS ≥1 year and OS <1 year. Cut-offs of significant parameters were determined using receiver operating characteristic curve analysis. Survival patterns were compared by log-rank test and presented using Kaplan-Meier curves. Cox proportion hazard model was used to determine the independent prognostic marker for 1 year OS. RESULTS In univariate survival analysis, 3 first order texture parameters (i.e. mean, median, root mean square with hazard ratios [HRs] 2.509 [P = 0.034], 2.590 [P = 0.05], 2.509 [P = 0.034], respectively) and 6 s order texture parameters (i.e. mean, auto correlation, cluster prominence, cluster shade, sum average and sum variance with HRs 2.509 [P = 0.034], 2.509 [P = 0.034], 3.929 [0.007], 2.903 [0.018], 2.954 [0.016] and 2.906 [0.014], respectively) were significantly associated with 1 year OS in these patients. Among the metabolic parameters, only metabolic tumor volume whole-body was significantly associated with 1 year OS. In multivariate survival analysis, cluster prominence came out as the independent predictor of 1 year OS. CONCLUSION Texture analysis based on F-18 FDG PET/CT is potentially beneficial in the prediction of OS ≥1 year in NSCLC patients undergoing platinum-based chemotherapy as first-line treatment. Thus, can be used to stratify the patients which will not be benefitted with platinum-based chemotherapy and essentially needs to undergo some other therapy option.
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Affiliation(s)
| | | | - Anshul Sharma
- Department of Nuclear Medicine, AIIMS, New Delhi, India
| | | | - Anant Mohan
- Department of Pulmonary Medicine and Sleep Disorders, AIIMS, New Delhi, India
| | | | - Lalit Gupta
- Department of Radio Diagnosis, AIIMS, New Delhi, India
| | - Shiba Kalyan Biswal
- Department of Pulmonary Medicine and Sleep Disorders, AIIMS, New Delhi, India
| | - Rakesh Kumar
- Department of Nuclear Medicine, AIIMS, New Delhi, India
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Kikuchi R, Takoi H, Tsuji T, Nagatomo Y, Tanaka A, Kinoshita H, Ono M, Ishiwari M, Toriyama K, Kono Y, Togashi Y, Yamaguchi K, Yoshimura A, Abe S. Glasgow Prognostic Score predicts chemotherapy-triggered acute exacerbation-interstitial lung disease in patients with non-small cell lung cancer. Thorac Cancer 2021; 12:667-675. [PMID: 33480111 PMCID: PMC7919129 DOI: 10.1111/1759-7714.13792] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 12/02/2020] [Accepted: 12/02/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Interstitial lung disease (ILD) in patients with non-small cell lung cancer (NSCLC) worsens the prognosis for overall survival (OS) due to chemotherapy-triggered acute exacerbation (AE)-ILD. The Glasgow Prognostic Score (GPS), which is based on serum C-reactive protein and albumin levels, has been suggested as a reliable prognostic tool for mortality in cancer patients, including NSCLC. In this study, we investigated whether GPS is a predictor for chemotherapy-triggered AE-ILD and the prognosis in patients with NSCLC and pre-existing ILD. METHODS We conducted a retrospective review on 56 NSCLC and ILD patients at our hospital who received platinum agent-based treatment as first-line chemotherapy between June 2010 and May 2019. We categorized these patients according to their GPS (0-2) and compared the incidence of chemotherapy-triggered AE-ILD and OS. RESULTS The GPS 0, 1, and 2 groups included 31, 16, and nine patients, respectively, out of 56. A total of 12 (21.4%) patients showed chemotherapy-triggered AE-ILD. The median OS was at 11.5 months (95% confidence interval: 8.0-15.1). The incidence of chemotherapy-triggered AE-ILD within the first year of chemotherapy in the GPS 0, 1, and 2 groups was three (9.6%), four (25.0%), and five (55.5%), and the median OS time was 16.9, 9.8 and 7.6 months, respectively. Univariate and multivariate analyses indicated that only GPS 2 could predict both chemotherapy-triggered AE-ILD and OS (P < 0.05). CONCLUSIONS GPS assessment of patients with NSCLC and pre-existing ILD is a valuable prognostic tool for predicting chemotherapy-triggered AE-ILD and OS. KEY POINTS SIGNIFICANT FINDINGS OF THE STUDY: We found that GPS 2 was an independent risk factor for chemotherapy-triggered AE-ILD and prognosis in patients with ILD associated with NSCLC. WHAT THIS STUDY ADDS GPS may potentially enable the discrimination of patients tolerant of chemotherapy from those at an increased risk of AE-ILD and predict the prognosis in patients with NSCLC and ILD receiving chemotherapy.
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Affiliation(s)
- Ryota Kikuchi
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Hiroyuki Takoi
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Takao Tsuji
- Respiratory Center, Otsuki Municipal Central Hospital, Yamanashi, Japan
| | - Yoko Nagatomo
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Akane Tanaka
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Hayato Kinoshita
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Mariko Ono
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Mayuko Ishiwari
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Kazutoshi Toriyama
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Yuta Kono
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Yuki Togashi
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Kazuhiro Yamaguchi
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Akinobu Yoshimura
- Department of Clinical Oncology, Tokyo Medical University Hospital, Tokyo, Japan
| | - Shinji Abe
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
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Gessner C, Potthoff K, Frost N. Efficacy and Safety of Lipegfilgrastim in Lung Cancer Patients Receiving Myelosuppressive Chemotherapy in a Real-World Setting: Results of an Analysis of Pooled Data from Two Non-Interventional European Studies. Oncol Res Treat 2021; 44:93-102. [PMID: 33477145 DOI: 10.1159/000512594] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 10/22/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIM Chemotherapy-induced neutropenia is a common and serious complication in cancer patients receiving myelosuppressive chemotherapy. This analysis was undertaken to evaluate the effectiveness and safety of prophylaxis with lipegfilgrastim, a glycoPEGylated granulocyte colony-stimulating factor, in lung cancer patients undergoing chemotherapy in real-world clinical practice. METHODS Data from two European non-interventional studies (NIS NADIR and NIS LEOS) investigating lipegfilgrastim for primary and secondary prophylaxis were pooled. Outcomes included the incidence of chemotherapy-induced neutropenia and febrile neutropenia (FN), use of anti-infectives and antimycotics, and adverse events and their relationship to lipegfilgrastim. RESULTS The safety population included 361 patients with lung cancer (median age, 66 years [range, 36-88]), of whom 322 had received 2 or more consecutive cycles of lipegfilgrastim (efficacy population [primary prophylaxis, 75.5%; secondary prophylaxis, 16.5%]). Almost 40% of the patients were considered to have a high risk (>20%) of FN, and around 60% had an intermediate risk (10-20%). For all cycles, FN was reported in 3 patients (0.9%), neutropenia in 14 (4.3%), and grade 4 neutropenia in 9 (2.8%). Anti-infectives were used in 27 patients (8.4%) and antimycotics in 6 (1.9%). The incidence rates were lower for the patients' first cycle (FN, 0.4%; neutropenia, 0.8%; grade 4 neutropenia, 0.8%; anti-infectives, 0.6%; antimycotics, 0.6%). Adverse drug reactions considered lipegfilgrastim related were reported in 35 patients (9.7%), and serious adverse drug reactions in 10 (2.8%). None of the fatal events reported in 28 patients (7.8%) were lipegfilgrastim related. CONCLUSION Lipegfilgrastim administered to patients with lung cancer undergoing chemotherapy in real-world clinical practice showed similar effectiveness and safety to that reported in published pivotal trials.
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Affiliation(s)
| | | | - Nikolaj Frost
- Department of Infectious Diseases and Pneumonology, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Bae JH, Baek YH, Lee JE, Song I, Lee JH, Shin JY. Machine Learning for Detection of Safety Signals From Spontaneous Reporting System Data: Example of Nivolumab and Docetaxel. Front Pharmacol 2021; 11:602365. [PMID: 33628176 PMCID: PMC7898680 DOI: 10.3389/fphar.2020.602365] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 11/02/2020] [Indexed: 12/14/2022] Open
Abstract
Introduction: Various methods have been implemented to detect adverse drug reaction (ADR) signals. However, the applicability of machine learning methods has not yet been fully evaluated. Objective: To evaluate the feasibility of machine learning algorithms in detecting ADR signals of nivolumab and docetaxel, new and old anticancer agents. Methods: We conducted a safety surveillance study of nivolumab and docetaxel using the Korea national spontaneous reporting database from 2009 to 2018. We constructed a novel input dataset for each study drug comprised of known ADRs that were listed in the drug labels and unknown ADRs. Given the known ADRs, we trained machine learning algorithms and evaluated predictive performance in generating safety signals of machine learning algorithms (gradient boosting machine [GBM] and random forest [RF]) compared with traditional disproportionality analysis methods (reporting odds ratio [ROR] and information component [IC]) by using the area under the curve (AUC). Each method then was implemented to detect new safety signals from the unknown ADR datasets. Results: Of all methods implemented, GBM achieved the best average predictive performance (AUC: 0.97 and 0.93 for nivolumab and docetaxel). The AUC achieved by each method was 0.95 and 0.92 (RF), 0.55 and 0.51 (ROR), and 0.49 and 0.48 (IC) for respective drug. GBM detected additional 24 and nine signals for nivolumab and 82 and 76 for docetaxel compared to ROR and IC, respectively, from the unknown ADR datasets. Conclusion: Machine learning algorithm based on GBM performed better and detected more new ADR signals than traditional disproportionality analysis methods.
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Affiliation(s)
- Ji-Hwan Bae
- School of Pharmacy, Sungkyunkwan University, Suwon-si, South Korea
| | - Yeon-Hee Baek
- School of Pharmacy, Sungkyunkwan University, Suwon-si, South Korea
| | - Jeong-Eun Lee
- School of Pharmacy, Sungkyunkwan University, Suwon-si, South Korea
| | - Inmyung Song
- Department of Health Administration, College of Nursing and Health, Kongju National University, Gongju-si, South Korea
| | - Jee-Hyong Lee
- Department of Artificial Intelligence, Sungkyunkwan University, Suwon-si, South Korea
| | - Ju-Young Shin
- School of Pharmacy, Sungkyunkwan University, Suwon-si, South Korea.,Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Jongno-gu, South Korea
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Docetaxel: An update on its molecular mechanisms, therapeutic trajectory and nanotechnology in the treatment of breast, lung and prostate cancer. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2020.101959] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Gkika E, Lenz S, Schimek-Jasch T, Waller CF, Kremp S, Schaefer-Schuler A, Mix M, Küsters A, Tosch M, Hehr T, Eschmann SM, Bultel YP, Hass P, Fleckenstein J, Thieme AH, Stockinger M, Dieckmann K, Miederer M, Holl G, Rischke HC, Adebahr S, König J, Binder H, Grosu AL, Nestle U. Efficacy and Toxicity of Different Chemotherapy Protocols for Concurrent Chemoradiation in Non-Small Cell Lung Cancer-A Secondary Analysis of the PET Plan Trial. Cancers (Basel) 2020; 12:cancers12113359. [PMID: 33202825 PMCID: PMC7697287 DOI: 10.3390/cancers12113359] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 11/01/2020] [Accepted: 11/05/2020] [Indexed: 12/14/2022] Open
Abstract
Simple Summary Concurrent chemoradiation (cCRT) with a platinum-based doublet, followed by immunotherapy, is the treatment of choice in locally advanced non-small cell lung cancer. A remaining open question is the difference between cisplatin and carboplatin in combination with second and third generation agents for concurrent chemoradiation, as they have a substantially different toxicity profile and data are scarce and inconclusive concerning cCRT. We here present a secondary analysis of the international PET Plan trial in order to assess the efficacy and toxicity of different chemotherapy regimens as well as the difference between the commonly used platinum based agents, cisplatin and carboplatin. All regimens were well tolerated and cisplatin in combination with vinorelbin either as a single dose or daily doses per cycle showed comparable efficacy. Patients treated with carboplatin doublets had a worse survival, but after adjusting for possibly relevant factors, this difference became non-significant, probably due to existing selection bias. Abstract (1) Background: The optimal chemotherapy (CHT) regimen for concurrent chemoradiation (cCRT) is not well defined. In this secondary analysis of the international randomized PET-Plan trial, we evaluate the efficacy of different CHT. (2) Methods: Patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume definition and received isotoxically dose-escalated cCRT using cisplatin 80 mg/m2 (day 1, 22) and vinorelbin 15 mg/m2 (day 1, 8, 22, 29) (P1) or cisplatin 20 mg/m2 (day 1–5, 29–33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P2) or carboplatin AUC1 (day 1–5, 29–33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P3) or other CHT at the treating physician’s discretion. (3) Results: Between 05/2009 and 11/2016, 205 patients were randomized and 172 included in the per-protocol analysis. Patients treated in P1 or P2 had a better overall survival (OS) compared to P3 (p = 0.015, p = 0.01, respectively). Patients treated with carboplatin had a worse OS compared to cisplatin (HR 1.78, p = 0.03), but the difference did not remain significant after adjusting for age, ECOG, cardiac function creatinine and completeness of CHT. (4) Conclusions: Carboplatin doublets show no significant difference compared to cisplatin, after adjusting for possibly relevant factors, probably due to existing selection bias.
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Affiliation(s)
- Eleni Gkika
- Department of Radiation Oncology, Medical Center—University of Freiburg, Robert-Koch-Str. 3, 79106 Freiburg, Germany; (T.S.-J.); (H.C.R.); (S.A.); (A.-L.G.); (U.N.)
- German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (DKFZ), Neuenheimer Feld 280, 69120 Heidelberg, Germany
- Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; (C.F.W.); (M.M.)
- Correspondence: ; Tel.: +49-(0)-761-95371
| | - Stefan Lenz
- Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, 79106 Freiburg, Germany; (S.L.); (H.B.)
| | - Tanja Schimek-Jasch
- Department of Radiation Oncology, Medical Center—University of Freiburg, Robert-Koch-Str. 3, 79106 Freiburg, Germany; (T.S.-J.); (H.C.R.); (S.A.); (A.-L.G.); (U.N.)
- German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (DKFZ), Neuenheimer Feld 280, 69120 Heidelberg, Germany
| | - Cornelius F. Waller
- Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; (C.F.W.); (M.M.)
- Department of Medicine I, Hematology, Oncology and Stem Cell Transplantation, Medical Center-University of Freiburg, 79106 Freiburg, Germany
| | - Stephanie Kremp
- Department of Radiotherapy and Radiation Oncology, Saarland University Medical Center and Faculty of Medicine, 66421 Homburg/Saar, Germany; (S.K.); (J.F.)
| | - Andrea Schaefer-Schuler
- Department of Nuclear Medicine, Saarland University Medical Center and Faculty of Medicine, 66421 Homburg/Saar, Germany;
| | - Michael Mix
- Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; (C.F.W.); (M.M.)
- Department of Nuclear Medicine, Medical Center—University of Freiburg, 79106 Freiburg, Germany
| | - Andreas Küsters
- Department of Radiation Oncology, Kliniken Maria Hilf, 41063 Mönchengladbach, Germany;
| | - Marco Tosch
- Department of Nuclear Medicine, Helios University Hospital Wuppertal, 42283 Wuppertal, Germany;
- Department of Medicine, Faculty of Health, University of Witten/Herdecke, 58448 Witten, Germany
| | - Thomas Hehr
- Department of Radiation Oncology, Marienhospital, 70199 Stuttgart, Germany;
| | | | - Yves-Pierre Bultel
- Department of Radiation Oncology, Klinikum Mutterhaus der Boromäerinnen, 54290 Trier, Germany;
| | - Peter Hass
- Department of Radiation Oncology, University Hospital Magdeburg, 39120 Magdeburg, Germany;
| | - Jochen Fleckenstein
- Department of Radiotherapy and Radiation Oncology, Saarland University Medical Center and Faculty of Medicine, 66421 Homburg/Saar, Germany; (S.K.); (J.F.)
| | - Alexander Henry Thieme
- Department of Radiation Oncology, Charité—Universitätsmedizin Berlin, 13353 Berlin, Germany;
| | - Marcus Stockinger
- Department of Radiation Oncology, University Hospital Mainz, 55131 Mainz, Germany;
| | - Karin Dieckmann
- Department of Radiotherapy, Vienna General Hospital, Medical University of Vienna, 1090 Vienna, Austria;
| | - Matthias Miederer
- Department of Nuclear Medicine, University Hospital Mainz, 55131 Mainz, Germany;
| | - Gabriele Holl
- Department of Nuclear Medicine, Kliniken Schwerin, 19055 Schwerin, Germany;
| | - Hans Christian Rischke
- Department of Radiation Oncology, Medical Center—University of Freiburg, Robert-Koch-Str. 3, 79106 Freiburg, Germany; (T.S.-J.); (H.C.R.); (S.A.); (A.-L.G.); (U.N.)
- Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; (C.F.W.); (M.M.)
- Department of Nuclear Medicine, Medical Center—University of Freiburg, 79106 Freiburg, Germany
| | - Sonja Adebahr
- Department of Radiation Oncology, Medical Center—University of Freiburg, Robert-Koch-Str. 3, 79106 Freiburg, Germany; (T.S.-J.); (H.C.R.); (S.A.); (A.-L.G.); (U.N.)
- German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (DKFZ), Neuenheimer Feld 280, 69120 Heidelberg, Germany
| | - Jochem König
- Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Hospital of Mainz, 55131 Mainz, Germany;
| | - Harald Binder
- Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, 79106 Freiburg, Germany; (S.L.); (H.B.)
| | - Anca-Ligia Grosu
- Department of Radiation Oncology, Medical Center—University of Freiburg, Robert-Koch-Str. 3, 79106 Freiburg, Germany; (T.S.-J.); (H.C.R.); (S.A.); (A.-L.G.); (U.N.)
- German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (DKFZ), Neuenheimer Feld 280, 69120 Heidelberg, Germany
- Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; (C.F.W.); (M.M.)
| | - Ursula Nestle
- Department of Radiation Oncology, Medical Center—University of Freiburg, Robert-Koch-Str. 3, 79106 Freiburg, Germany; (T.S.-J.); (H.C.R.); (S.A.); (A.-L.G.); (U.N.)
- German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (DKFZ), Neuenheimer Feld 280, 69120 Heidelberg, Germany
- Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; (C.F.W.); (M.M.)
- Department of Radiation Oncology, Kliniken Maria Hilf, 41063 Mönchengladbach, Germany;
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DaCosta Byfield S, Chastek B, Korrer S, Horstman T, Malin J, Newcomer L. Real-World Outcomes and Value of First-Line Therapy for Metastatic Non-Small Cell Lung Cancer †. Cancer Invest 2020; 38:608-617. [PMID: 33107767 DOI: 10.1080/07357907.2020.1827415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Although physicians rely on clinical trial data to guide cancer treatment decisions, patient characteristics and outcomes often differ between real-world and clinical trial populations. We analyzed retrospective clinical data collected from a prior authorization (PA) tool linked with payer claims data to describe outcomes of first-line treatment for metastatic non-small cell lung cancer among 2,108 patients. Duration of therapy was shorter than observed in clinical trials. Healthcare costs and hospitalizations varied substantially by regimen. PA clinical data linked with administrative claims enable head-to-head comparisons of contemporary cancer treatments used in routine clinical practice, which are not available from clinical trials.
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Affiliation(s)
| | | | | | | | | | - Lee Newcomer
- Lee N. Newcomer Consulting, LLC, Minneapolis, Minnesota, USA
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Morita-Ogawa T, Sugita H, Minami H, Yamaguchi T, Hanada K. Population pharmacokinetics and renal toxicity of cisplatin in cancer patients with renal dysfunction. Cancer Chemother Pharmacol 2020; 86:559-566. [PMID: 32949266 DOI: 10.1007/s00280-020-04147-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 09/08/2020] [Indexed: 12/19/2022]
Abstract
PURPOSE The pharmacokinetics (PKs) of cisplatin have not been investigated in patients with renal dysfunction, characterized by creatinine clearance (Ccr) < 60 mL/min. In this study, we performed a population pharmacokinetic (PPK) analysis of unchanged cisplatin in patients with renal dysfunction. We investigated the effects of renal dysfunction on the PKs and nephrotoxicity of unchanged cisplatin. METHODS We enrolled 23 patients with moderate renal dysfunction (Ccr calculated to be 30-60 mL/min using the Cockcroft-Gault formula) treated with cisplatin. PPK analysis was performed by nonlinear mixed effect modeling using NONMEM (Version 7.2). We evaluated gender, age, body surface area (BSA), weight, baseline Ccr, baseline serum creatinine (Scr), and baseline urea nitrogen as potential covariates. The final model was evaluated using bootstrap analysis. Renal toxicity was evaluated using Common Terminology Criteria for Adverse Events ver. 4.0. The frequency of severe renal dysfunction (Grade 3/4 Scr elevation) was measured in the population. RESULTS A one-compartment model adequately described the unchanged cisplatin data. The population mean values for clearance (CLtot) and volume of distribution (Vd) were 19.1 L/h [coefficient of variation (CV) 19.4%] and 13.8 L (CV 41.0%), respectively. The final model identified BSA as a significant covariate for CLtot. There were no significant covariates for Vd. No patients suffered from severe nephrotoxicity to the point that hemodialysis was required. CONCLUSION Moderate renal dysfunction does not affect the PKs of unchanged cisplatin. The increased serum concentration of cisplatin may not lead to increased toxicity in patients with renal dysfunction. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION UMIN000007091 (January 17, 2012).
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Affiliation(s)
- Tomoko Morita-Ogawa
- Department of Pharmacometrics and Pharmacokinetics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan.
| | - Hiroki Sugita
- Department of Pharmacometrics and Pharmacokinetics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan
| | - Hironobu Minami
- Division of Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital and Graduate School of Medicine, Hyogo, Japan
| | - Takuhiro Yamaguchi
- Division of Biostatistics, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Kazuhiko Hanada
- Department of Pharmacometrics and Pharmacokinetics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan
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Li LJ, Chong Q, Wang L, Cher GB, Soo RA. Different treatment efficacies and side effects of cytotoxic chemotherapy. J Thorac Dis 2020; 12:3785-3795. [PMID: 32802458 PMCID: PMC7399437 DOI: 10.21037/jtd.2019.08.63] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Differences in efficacy and toxicity between Asian and Caucasian patients with lung cancer treated with systemic chemotherapy is increasingly recognised. This is a major concern in the clinical setting as it influences outcomes and affect international harmonization of drug development. Interindividual variability of pharmacokinetics, where different genetic polymorphisms affect drug metabolism, transport, and receptor binding may account for the ethnic differences. Treatment efficacy and outcomes may also be explained by differences in diet and lifestyle, access to healthcare, cultural barriers and environmental exposure. Efforts made to design prospective studies investigating ethnic specific determinants to systemic therapy and individualise lung cancer treatment based on genetic makeup of patient are important.
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Affiliation(s)
- Low-Jia Li
- Department of Haematology-Oncology, National University Hospital, Singapore, Singapore
| | - Qingyun Chong
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
| | - Lingzhi Wang
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.,Department of Pharmacology, National University of Singapore, Singapore, Singapore
| | - Goh Boon Cher
- Department of Haematology-Oncology, National University Hospital, Singapore, Singapore.,Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.,Department of Pharmacology, National University of Singapore, Singapore, Singapore
| | - Ross A Soo
- Department of Haematology-Oncology, National University Hospital, Singapore, Singapore
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Sun M, Zhou T, Fang X, Wang D, Pang H, Chen Y, Hu K. A multicenter randomized controlled trial to assess the efficacy of cancer green therapy in treatment of stage IIIb/IV non-small cell lung cancer. Medicine (Baltimore) 2020; 99:e21626. [PMID: 32872022 PMCID: PMC7437773 DOI: 10.1097/md.0000000000021626] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 07/08/2020] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Chemotherapy is the main therapy for stage IIIB/IV non-small cell lung cancer (NSCLC). However, the 5-year survival rate is 6%. Cancer Green Therapy is a novel therapy in China, which refers to cryoablation combined with traditional Chinese medicine (TCM) formula. Our previous retrospective analysis showed that patients with NSCLC had longer survival time and better quality of life after receiving cryoablation combined with TCM formula, compared with patients who received chemotherapy alone. METHODS This study is a multicenter, randomized, controlled clinical study. The experiment will be carried out in 6 hospitals at the same time, and a total of 450 cases of participants will be randomly assigned to the experimental group and the control group (n = 225). The experimental group will be given cryoablation and 28-days TCM formula, and the control group will be given 4 cycles chemotherapy. After 30 months of follow-up, the efficacy and safety of cryoablation combines with TCM formula in patients with stage IIIB/IV NSCLC will be observed. The primary outcome is overall survival. The secondary outcomes include progression-free survival, objective response rate, and quality of life. We will also conduct a safety evaluation of the treatment at the end of the trial. DISCUSSION This multicenter, randomized, controlled clinical study not only provides data on the efficacy and safety of cryoablation combined with TCM formula, but also provides a novel treatment strategy for clinicians and advanced NSCLC patients.
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Sakin A, Sahin S, Mustafa Atci M, Yasar N, Demir C, Geredeli C, Sakin A, Cihan S. The Effect of Body Mass Index on Treatment Outcomes in Patients with Metastatic Non-Small Cell Lung Cancer Treated with Platinum-Based Therapy. Nutr Cancer 2020; 73:1411-1418. [PMID: 32748654 DOI: 10.1080/01635581.2020.1801774] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
To investigate the effect of body mass index(BMI) on treatment outcomes and side-effect profile in metastatic non-small cell lung cancer(NSCLC) patients receiving platinum-based chemotherapy(ChT) in the first-line setting. This was a retrospective analysis of 233 NSCLC patients who were treated and followed up from 2008 through 2018. NSCLC patients who had metastatic disease at the time of diagnosis and were treated with platinum-based ChT in the first-line setting were included. The patients were divided into 2 groups based on the BMI as follows; BMI < 25 kg/m2 and BMI ≥ 25 kg/m2. This retrospective analysis enrolled 233 patients, 35 (15.0%) of whom were female. The BMI in 132 patients (56.2%) was < 25 kg/m2. The median age was 58 years (range, 21-90). Median progression-free survival(PFS) was 7 mo, in the patients with BMI ≥ 25 kg/m2 compared to 5.0 mo, in those with BMI < 25 kg/m2 (p = 0.032), with corresponding median overall survival(OS) durations of 12 vs. 9 mo, (p = 0.003). In multivariate analysis, ECOG PS 2, grade III histology, and brain or bone metastasis negatively affected OS, whereas BMI ≥ 25 kg/m2 positively affected OS. A high BMI prior to therapy in patients with NSCLC treated with platinum-based ChT in the first-line setting was associated with more favorable PFS and OS.
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Affiliation(s)
- Aysegul Sakin
- Department of Internal Medicine, University of Health Sciences, Van Training and Research hospital, Van, Turkey
| | - Suleyman Sahin
- Department of Medical Oncology, University of Health Sciences, Van Research and Training Hospital, Van, Turkey
| | - Muhammed Mustafa Atci
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Nurgul Yasar
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Cumhur Demir
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Caglayan Geredeli
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Abdullah Sakin
- Department of Medical Oncology, Yuzuncu Yil University Medical School, Van, Turkey
| | - Sener Cihan
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
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Swithenbank L, Cox P, Harris LG, Dudley E, Sinclair K, Lewis P, Cappiello F, Morgan C. Temporin A and Bombinin H2 Antimicrobial Peptides Exhibit Selective Cytotoxicity to Lung Cancer Cells. SCIENTIFICA 2020; 2020:3526286. [PMID: 32676212 PMCID: PMC7341413 DOI: 10.1155/2020/3526286] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 05/21/2020] [Accepted: 05/30/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Recently, antimicrobial peptides (AMPs) have been investigated for their use in cancer therapy. They have been reported to selectively target and kill cancer cells whilst leaving normal healthy cells unaffected. Certain Anura AMPs have expressed selective cytotoxicity against tumour cells. AIM To test the potential of Anura AMPs bombinin H2, bombinin H4, temporin A, and temporin L for use as therapeutic agents for non-small cell lung carcinoma (NSCLC). METHODS Cytotoxic effects on NSCLC cell lines A549 and Calu-3 and normal epithelial cell line Beas-2B were tested using the CellTox Green Cytotoxicity Assay. Their haemolytic effects on human erythrocytes were also tested for their clinical relevance. Cell membrane profiling, using MALDI-TOF, was performed to ascertain if membrane characteristics of the NSCLC and Beas-2B cell lines may contribute to the AMPs mode of action. RESULTS Bombinin H4 (100-1.5 μM, p < 0.05) and temporin A (100-50 μM, p < 0.05) showed selective cytotoxicity towards the NSCLC cell lines. Furthermore, they exhibited low levels of haemolytic activity (bombinin H4, 0.061%; temporin A, 0.874%) comparable to untreated cells. Cell membrane profiling showed the phospholipid composition of normal epithelial cell line Beas-2B to be divergent from the cancerous cell lines. However, there was an overlap in the phospholipid profiles of the NSCLC cell lines supporting the hypothesis that the AMPs may have a selective affinity via the membrane composition of cancerous cell lines. CONCLUSION These results suggest that bombinin H4 and temporin A show potential for application in lung cancer therapies. Further in vitro and in vivo studies are required to develop a greater understanding of their use as anticancer agents.
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Affiliation(s)
- Lucy Swithenbank
- Swansea University Medical School, Institute of Life Science, Swansea University, Swansea SA2 8PP, UK
| | - Phillipa Cox
- Swansea University Medical School, Institute of Life Science, Swansea University, Swansea SA2 8PP, UK
| | - Llinos G. Harris
- Swansea University Medical School, Institute of Life Science, Swansea University, Swansea SA2 8PP, UK
| | - Edward Dudley
- Swansea University Medical School, Institute of Life Science, Swansea University, Swansea SA2 8PP, UK
| | - Kathryn Sinclair
- Swansea University Medical School, Institute of Life Science, Swansea University, Swansea SA2 8PP, UK
| | - Paul Lewis
- Swansea University Medical School, Institute of Life Science, Swansea University, Swansea SA2 8PP, UK
| | - Floriana Cappiello
- Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Rome, Italy
| | - Claire Morgan
- Swansea University Medical School, Institute of Life Science, Swansea University, Swansea SA2 8PP, UK
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Morales ASR, Joy JK, Zbona DM. Administration sequence for multi-agent oncolytic regimens. J Oncol Pharm Pract 2020; 26:933-942. [DOI: 10.1177/1078155219895070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Purpose The existence of a multitude of oncolytics regimens containing two or more agents (combination) outlines the need to define their most adequate sequence of administration. However, limited resources are currently available to specify a particular sequence, presenting challenges potentially impacting on patient safety, and Pharmacy & Infusion Nursing workflows. Methods A comprehensive literature search was performed leading to the compilation of a document containing drug administration sequencing instructions for our Nursing, Pharmacy, and Oncology providers to follow. Regimens prioritized in our literature review represented regimens selected as part of our approved Clinical Pathways, regimens inquiries from Pharmacy or Nursing, as well as less frequently used regimens. We stratified the regimens by tumor type and arranged them alphabetically by indication. Results A table was compiled containing all the supporting literature for the recommended drug administration sequences. If, in certain instances, no literature support was identified outlining rationale such as enhanced management of adverse effects, a specific institutional decision was made by our enterprise Medical Oncology Committee with recommendations from Pharmacy experts. The primary guiding principles for outlining our recommendations were the following: administration of vesicant agents first; administration of biologic agents first; administration of taxanes prior to platinum agents; and duration of infusion (shorter infusions prioritized). Conclusion This guideline is not exhaustive. The compilation provided here is intended to be utilized as guidance for oncolytics administration sequence. We will continue to review and incorporate treatment sequencing recommendations for additional regimens.
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Affiliation(s)
| | - Jamie K Joy
- Cancer Treatment Centers of America Global, Boca Raton, FL, USA
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Nobili S, Lavacchi D, Perrone G, Vicini G, Tassi R, Landini I, Grosso A, Roviello G, Mazzanti R, Santomaggio C, Mini E. Vinorelbine in Non-Small Cell Lung Cancer: Real-World Data From a Single-Institution Experience. Oncol Res 2020; 28:237-248. [PMID: 31806078 PMCID: PMC7851511 DOI: 10.3727/096504019x15755437099308] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
The use of vinorelbine as a single agent or in combination regimens in non-small cell lung cancer (NSCLC) is associated with satisfactory clinical activity. However, the role of vinorelbine-based chemotherapy in chemonaive locally advanced unresectable or metastatic NSCLC patients, according to real-world treatment patterns, has still not been widely explored. Eighty-one patients treated at a single institution were retrospectively analyzed. Thirty-seven received standard first-line single-agent vinorelbine, and 44 received vinorelbine plus platinum drugs, based on physician's choice; 61.7% were older than 70 years, and 60.5% were affected by ≥2 comorbidities. Sixty-three patients were evaluable for objective response: 22% achieved partial response and 41% stable disease. Median progression-free survival (PFS) was 5.4 months. A benefit in PFS was observed in patients treated with combinations vs. single-agent vinorelbine (6.7 vs. 3.5 months, p = 0.043). Median overall survival (OS) was 10.4 months without a statistically significant difference between treatments (12.4 vs. 7.5 months). In 55 stage IV patients, OS was positively correlated with combination regimens, M1a stage, or ≤2 metastatic lesions. Grade 3-4 toxicity occurred in 33% of patients, and dose reduction in 11%. A statistically significant higher incidence of toxicity was observed in patients receiving combinations, in women, in patients younger than 75 years, or patients with metastases. In this real-word analysis, we confirmed the efficacy and tolerability of vinorelbine as a single agent or combined with platinums in patients usually underrepresented in controlled clinical trials. Single-agent vinorelbine may represent a suitable option in elderly or unfit NSCLC patients and warrants investigation as a potential drug candidate for immunochemotherapy combination regimens.
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Affiliation(s)
- Stefania Nobili
- *Section of Clinical Pharmacology and Oncology, Department of Health Science, University of Florence, Florence, Italy
| | - Daniele Lavacchi
- †School of Human Health, University of Florence, Florence, Italy
| | - Gabriele Perrone
- *Section of Clinical Pharmacology and Oncology, Department of Health Science, University of Florence, Florence, Italy
| | - Giulio Vicini
- †School of Human Health, University of Florence, Florence, Italy
| | - Renato Tassi
- ‡Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Ida Landini
- *Section of Clinical Pharmacology and Oncology, Department of Health Science, University of Florence, Florence, Italy
| | - AnnaMaria Grosso
- §Unit of Pneumology and Thoracic-Pulmonary Physiopathology, Careggi University Hospital, Florence, Italy
| | - Giandomenico Roviello
- *Section of Clinical Pharmacology and Oncology, Department of Health Science, University of Florence, Florence, Italy
- ¶Unit of Translational Oncology, Careggi University Hospital, Florence, Italy
| | - Roberto Mazzanti
- ‡Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Carmine Santomaggio
- ¶Unit of Translational Oncology, Careggi University Hospital, Florence, Italy
| | - Enrico Mini
- *Section of Clinical Pharmacology and Oncology, Department of Health Science, University of Florence, Florence, Italy
- ¶Unit of Translational Oncology, Careggi University Hospital, Florence, Italy
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Jiang W, Zeng A, Ning R, Zhao W, Su C, Wang H, Zhou S, Yu Q. Predictive value of tumor genetic alteration profiling for chemotherapy and EGFR-TKI treatment in advanced NSCLC. Oncol Lett 2020; 19:3859-3870. [PMID: 32382334 PMCID: PMC7202306 DOI: 10.3892/ol.2020.11502] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Accepted: 02/14/2020] [Indexed: 01/05/2023] Open
Abstract
Previous studies have suggested that a variety of tumor driver genetic alterations affected the treatment efficacy of chemotherapy and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). The present study aimed to investigate the association between the tumor genetic alteration landscape and the treatment outcome of first-line chemotherapy and EGFR-TKIs in advanced NSCLC. A total of 94 patients with advanced NSCLC were recruited. All patients received first-line chemotherapy and/or EGFR-TKIs (either first- or second-generation EGFR-TKI, or third-generation EGFR-TKI) alone or sequentially. Prior to chemotherapy and/or EGFR-TKI treatment, plasma, effusion and/or tumor tissues from the included patients were subjected to next-generation sequencing, targeting 59 genes. The results indicated that the positive genetic alteration status prior to first-line chemotherapy was associated with prolonged progression-free survival (PFS) time compared with the negative status [9.1 vs. 4.0 months; hazard ratio (HR)=6.68; 95% CI, 2.25–19.82; P=0.001). Furthermore, patients with EGFR activating mutation harboring concomitant alterations exhibited a shorter PFS (11.1 vs. 7.4 months; HR=2.14; 95% CI, 1.03–4.44; P=0.04) and overall survival (OS) time [not reached (NR) vs. 32.8 months; HR=4.30; 95% CI, 1.41–13.16; P=0.01] than those without concomitant alterations, with first- and second-generation EGFR-TKI treatment. Similarly, patients with T79M mutation harboring concomitant alterations exhibited a shorter PFS (15.6 vs. 3.6 months; HR=9.48; 95% CI, 2.29–39.28; P=0.002) and OS time (NR vs. 32.8 months; HR=4.85; 95% CI, 1.16–20.29; P=0.03) with osimertinib treatment. Taken together, the results demonstrated that positive genetic alteration status predicted greater efficacy of first-line chemotherapy, while concomitant genetic alterations were associated with poor treatment outcome for first- or second-generation EGFR-TKI and third-generation EGFR-TKI treatment.
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Affiliation(s)
- Wei Jiang
- Department of Respiratory Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Aiping Zeng
- Department of Respiratory Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Ruiling Ning
- Department of Respiratory Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Wenhua Zhao
- Department of Respiratory Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Cuiyun Su
- Department of Respiratory Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Huilin Wang
- Department of Respiratory Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Shaozhang Zhou
- Department of Respiratory Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Qitao Yu
- Department of Respiratory Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
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Jose WM. Taxanes – The Backbone of Medical Oncology. Indian J Med Paediatr Oncol 2020. [DOI: 10.4103/ijmpo.ijmpo_1_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
AbstractDrug development in oncology has witnessed a revolutionary growth from its humble beginning with nitrogen mustard in 1940 to immunotherapy in 1986 (Interferon alpha). The arsenal of cytotoxics is ever increasing, contributing to better survival outcomes and improved quality of life. Over the years, many cytotoxics have fallen out of favor too, due to its side effects and availability of drugs with better efficacy and toxicity profile. Taxane, a microtubule stabilizing agent extracted from the poisonous Yew tree, was discovered in 1964 and came into clinical use in 1992 with its approval for ovarian cancer. This group has grown into a cornerstone of many treatment protocols, spanning multiple tumor types. This review discusses in brief the salient features of cytotoxic agents in this drug group, its history, physico-chemical properties, mechanism of action, pharmacodynamics, and pharmacokinetics. Though the benefits of taxanes are well understood, there are unique problems associated with the use of taxanes and there is an expanding literature on taxane resistance. We briefly look at the resistance mechanisms. There have been significant efforts to circumvent the problems related to conventional taxanes, with an attempt at creating newer carrier molecules and adjunct drugs with taxanes, which is slowly gaining traction in clinical practice.
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Affiliation(s)
- Wesley M Jose
- Department of Medical Oncology and Hematology, Amrita Institute of Medical Sciences, Amrita Vishwavidyapeetham, Health Science Campus, Kochi, Kerala, India
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Vasconcellos VF, Marta GN, da Silva EMK, Gois AFT, de Castria TB, Riera R, Cochrane Lung Cancer Group. Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer. Cochrane Database Syst Rev 2020; 1:CD009256. [PMID: 31930743 PMCID: PMC6956680 DOI: 10.1002/14651858.cd009256.pub3] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in both sexes worldwide. Approximately 50% of those diagnosed with lung cancer will have locally advanced or metastatic disease and will be treated in a palliative setting. Platinum-based combination chemotherapy has benefits in terms of survival and symptom control when compared with best supportive care. OBJECTIVES To assess the effectiveness and safety of carboplatin-based chemotherapy when compared with cisplatin-based chemotherapy, both in combination with a third-generation drug, in people with advanced non-small cell lung cancer (NSCLC). To compare quality of life in people with advanced NSCLC receiving chemotherapy with cisplatin and carboplatin combined with a third-generation drug. SEARCH METHODS We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 13 January 2019), MEDLINE (via PubMed) (1966 to 13 January 2019), and Embase (via Ovid) (1974 to 13 January 2019). In addition, we handsearched the proceedings of the American Society of Clinical Oncology Meetings (January 1990 to September 2018) and reference lists from relevant resources. SELECTION CRITERIA Randomised clinical trials (RCTs) comparing regimens with carboplatin or cisplatin combined with a third-generation drug in people with locally advanced or metastatic NSCLC. We accepted any regimen and number of cycles that included these drugs, since there is no widely accepted standard regimen. DATA COLLECTION AND ANALYSIS Two review authors independently assessed the search results, and a third review author resolved any disagreements. The primary outcomes were overall survival and health-related quality of life. The secondary outcomes were one-year survival rate, objective response rate and toxicity. MAIN RESULTS In this updated review, we located one additional RCT, for a total of 11 included RCTs (5088 participants, 4046 of whom were available for meta-analysis). There was no difference in overall survival (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.82 to 1.20; 10 RCTs; 2515 participants; high-quality evidence); one-year survival rate (risk ratio (RR) 0.98, 95% CI 0.89 to 1.08; I2 = 17%; 4004 participants; all 11 RCTs; high-quality evidence); or response rate (RR 0.89, 95% CI 0.79 to 1.00; I2 = 12%; all 11 RCTs; 4020 participants; high-quality evidence). A subgroup analysis comparing carboplatin with different doses of cisplatin found an overall survival benefit in favour of carboplatin-based regimens when compared to cisplatin at lower doses (40 to 80 mg/m2) (HR 1.15, 95% CI 1.03 to 1.28; 6 RCTs; 2508 participants), although there was no overall survival benefit when carboplatin-based chemotherapy was compared to cisplatin at higher doses (80 to 100 mg/m2) (HR 0.93, 95% CI 0.83 to 1.04; I2 = 0%; 4 RCTs; 1823 participants). Carboplatin caused more thrombocytopenia (RR 2.46, 95% CI 1.49 to 4.04; I2 = 68%; 10 RCTs; 3670 participants) and was associated with more neurotoxicity (RR 1.42, 95% CI 0.91 to 2.23; I2 = 0%, 5 RCTs; 1489 participants), although we believe this last finding is probably related to a confounding factor (higher dose of paclitaxel in the carboplatin-containing treatment arm of a large study included in the analysis). There was no statistically significant difference in renal toxicity (RR 0.52, 95% CI 0.19 to 1.45; I2 = 3%; 3 RCTs; 1272 participants); alopecia (RR 1.11, 95% CI 0.73 to 1.68; I2 = 0%; 2 RCTs; 300 participants); anaemia (RR 1.37, 95% CI 0.79 to 2.38; I2 = 77%; 10 RCTs; 3857 participants); and neutropenia (RR 1.18, 95% CI 0.85 to 1.63; I2 = 94%; 10 RCTs; 3857 participants) between cisplatin-based chemotherapy and carboplatin-based chemotherapy regimens. Two RCTs performed a health-related quality of life analysis; however, as they used different methods of measurement we were unable to perform a meta-analysis. One RCT reported comparative health-related quality of life data between cisplatin and carboplatin-containing arms but found no significant differences in global indices of quality of life, including global health status or functional scales. In this Cochrane review, we found that the quality of evidence was high for overall survival, one-year survival rate and response rate but moderate quality evidence for the other outcomes measured. AUTHORS' CONCLUSIONS Advanced NSCL patients treated with carboplatin or cisplatin doublet with third-generation chemotherapy drugs showed equivalent overall survival, one-year survival, and response rate. Regarding adverse events, carboplatin caused more thrombocytopenia, and cisplatin caused more nausea/vomiting. Therefore, in this palliative therapeutic intent, the choice of the platin compound should take into account the expected toxicity profile, patient's comorbidities and preferences.
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Affiliation(s)
- Vitor F Vasconcellos
- Instituto do Câncer do Estado de São Paulo (ICESP/FMUSP)Medical OncologyAv. Dr Arnaldo 251São PauloSao PauloBrazil01246‐000
| | - Guilherme N Marta
- Instituto do Câncer do Estado de São Paulo (ICESP/FMUSP)Medical OncologyAv. Dr Arnaldo 251São PauloSao PauloBrazil01246‐000
| | - Edina MK da Silva
- Universidade Federal de São PauloEmergency Medicine and Evidence Based MedicineRua Borges Lagoa 564 cj 64Vl. ClementinoSão PauloSão PauloBrazil04038‐000
| | - Aecio FT Gois
- Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em SaúdeCochrane BrazilRua Pedro de Toledo, 598São PauloSão PauloBrazil04039‐001
| | - Tiago B de Castria
- Instituto do Câncer do Estado de São Paulo (ICESP/FMUSP)Medical OncologyAv. Dr Arnaldo 251São PauloSao PauloBrazil01246‐000
| | - Rachel Riera
- Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em SaúdeCochrane BrazilRua Pedro de Toledo, 598São PauloSão PauloBrazil04039‐001
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Li S, Zhang S, Liu J, Yang C, Zhang L, Cheng Y. The effect of PD-L1/PD-1 immunotherapy in the treatment of squamous non-small-cell lung cancer: a meta-analysis of randomized controlled clinical trials. J Thorac Dis 2020; 11:4453-4463. [PMID: 31903233 DOI: 10.21037/jtd.2019.11.12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Background This meta-analysis evaluated the efficacy of PD-L1/PD-1 immunotherapy compared with chemotherapy in IIIB or IV or recurrent squamous non-small cell lung cancer (NSCLC) patients. Methods We performed a literature search on the PubMed, EMBASE, Web of Science, and Cochrane databases, in addition to the abstracts from major conference proceedings of the European Society for Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and the World Conference on Lung Cancer (WCLC) from 2004 to May 2019. Randomized controlled trials that compared PD-L1/PD-1 immunotherapy with chemotherapy in IIIB or IV or recurrent squamous NSCLC were included. The endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), 1-y OS rate, and 1-y PFS rate. Results A total of 3,213 IIIB or IV or recurrent squamous NSCLC patients from 12 trials of high quality were included in this meta-analysis, among whom 1,677 were in the PD-L1/PD-1 immunotherapy group and 1,536 were in the chemotherapy group. The results indicated that compared with chemotherapy, immunotherapy significantly prolonged OS (HR =0.75; 95% CI, 0.68-0.83; P<0.001) and PFS (HR =0.66; 95% CI, 0.60-0.73; P<0.001) in patients with advanced squamous NSCLC. The pooled model showed that ORR, DCR, and 1-y PFS rate were also significantly higher with immunotherapy compared with chemotherapy (ORR: RR =1.43; 95% CI, 1.11-1.83; P=0.005; DCR: RR =1.14; 95% CI, 1.05-1.24; P=0.003; 1-y PFS rate: RR =2.30; 95% CI, 1.69-3.13; P<0.001). The 1-y OS rate tended to be higher in the immunotherapy group, but there was no significant difference compared with chemotherapy (RR =1.28; 95% CI, 0.95-1.72; P=0.104). Conclusions Our study proves that PD-L1/PD-1 immunotherapy can significantly improve OS, PFS, ORR, DCR, and 1-y PFS of metastatic squamous NSCLC patients compared with chemotherapy.
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Affiliation(s)
- Shuang Li
- Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun 130012, China
| | - Shuang Zhang
- Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun 130012, China
| | - Jingjing Liu
- Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun 130012, China
| | - Changliang Yang
- Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun 130012, China
| | - Liang Zhang
- Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun 130012, China
| | - Ying Cheng
- Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun 130012, China
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Survival Implications of De Novo Versus Recurrent Metastatic Non-Small Cell Lung Cancer. Am J Clin Oncol 2019; 42:292-297. [PMID: 30608237 DOI: 10.1097/coc.0000000000000513] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVES Metastatic non-small cell lung cancer (NSCLC) has a poor prognosis. Most patients present with stage IV, and many patients treated curatively with stage I to III develop recurrent metastatic disease. It is unknown whether the natural history differs between patients with recurrent versus de novo metastatic NSCLC. We hypothesized that de novo metastatic status is associated with decreased overall survival compared with recurrent metastatic disease. MATERIALS AND METHODS A retrospective review was completed of all patients with NSCLC referred to BC Cancer from 2005 to 2012. Two cohorts were created; de novo metastatic disease and patients treated with curative intent (surgery or radiotherapy) that developed recurrent, metastatic disease. Information was collected on known prognostic and predictive factors. Overall survival was calculated from the date of diagnosis of metastatic disease. RESULTS A total of 9651 patients were evaluated, 5782 (60%) with de novo stage IV disease, and 3869 (40%) with stage I to III disease. Of the 1658 patients who received curative therapy for stage I to III disease, 757 (46%) developed metastases. Patients in the de novo cohort versus recurrent cohort were more likely male (52% vs. 48%), have poorer performance status (Eastern Cooperative Oncology Group≥2 50% vs. 44%), and receive no palliative systemic therapy (67% vs. 61%). The median overall survival in the de novo cohort was 4.7 versus 6.9 m in the recurrent cohort (P<0.001). De novo status was associated with shorter overall survival and this remained significant in a multivariate model that incorporated known prognostic factors. CONCLUSIONS In a large population-based study of NSCLC, de novo metastatic status was independently associated with decreased overall survival from the time of metastatic disease diagnosis.
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Kubota K, Kunitoh H, Seto T, Shimada N, Tsuboi M, Ohhira T, Okamoto H, Masuda N, Maruyama R, Shibuya M, Watanabe K. Randomized phase II trial of adjuvant chemotherapy with docetaxel plus cisplatin versus paclitaxel plus carboplatin in patients with completely resected non-small cell lung cancer: TORG 0503. Lung Cancer 2019; 141:32-36. [PMID: 31931444 DOI: 10.1016/j.lungcan.2019.11.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 10/26/2019] [Accepted: 11/13/2019] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Adjuvant chemotherapy is standard of care for patients with completely resected stage IB, II and IIIA NSCLC. However, optimum chemotherapy regimen has not been determined. TORG0503 was undertaken to select a preferred platinum-based 3rd generation regimen in this clinical setting. MATERIALS AND METHODS Patients with completely resected stage IB, IIA, IIB or stage IIIA NSCLC were stratified by stage (IB/IIA vs. IIB/IIIA) and institutions, and randomized to receive 3 cycles of docetaxel (60 mg/m2) plus cisplatin (80 mg/m2) (arm A) or paclitaxel (200 mg/m2) plus carboplatin (AUC 6) (arm B) on day 1, every 3 weeks. The primary endpoint of the study was 2-year relapse free survival, and the key secondary endpoints included overall survival, feasibility and toxicity. RESULTS 111 patients were randomized, 58 patients to arm A and 53 to arm B. Patient demographics were balanced between the two arms. 93 % (54/58) of patients on the arm A and 92 % (49/53) patients on the arm B completed the planned 3 cycles of chemotherapy. There was no treatment-related death in both arms. The 2 and 5 year relapse free survival was 74.5 % (95 %CI: 68.6-80.4) and 61.6 % in the arm A, and 72.0 % (95 %CI: 65.7-78.3) and 46.0 % in the arm B. The overall 2, 5-year survival was 89.7 %, 73.9 % in the arm A and 86.9 %, 67.5 % in the arm B. CONCLUSION Both docetaxel plus cisplatin and paclitaxel plus carboplatin are safe and feasible regimens as adjuvant chemotherapy. We choose docetaxel plus cisplatin as the control regimen for the next clinical trial.
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Affiliation(s)
- Kaoru Kubota
- Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
| | - Hideo Kunitoh
- Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Internal Medicine, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Takashi Seto
- Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan
| | - Naoki Shimada
- Center for Medical Science, International University of Health and Welfare, Ohtawara, Japan
| | - Masahiro Tsuboi
- Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Department of Surgery, Tokyo Medical University Hospital, Tokyo, Japan
| | - Tatsuo Ohhira
- Department of Surgery, Tokyo Medical University Hospital, Tokyo, Japan
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Chen L, Kim JS, San Antonio B, Zhu YE, Mitchell L, John W. Safety outcomes in advanced non-small-cell lung cancer patients treated with first-line platinum-based regimens in the United States. J Thorac Dis 2019; 11:4474-4483. [PMID: 31903235 DOI: 10.21037/jtd.2019.11.11] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background We analyzed the treatment patterns and safety outcomes of the most common first-line platinum-based regimens initiated on or after non-small cell lung cancer (NSCLC) diagnosis in a real-world setting. Methods Based on a United States oncology electronic medical record (EMR) database, patients treated with first-line platinum-based regimens after advanced NSCLC diagnosis from September 2008 to November 2014 were analyzed. Baseline characteristics and selected adverse events during treatment [incidence proportions and incidence rates (IRs)] were described by regimen. Propensity score stratification was used to adjust for baseline characteristics differences. Hazard ratios (HRs) were estimated using Cox proportional hazards model, with paclitaxel (Pac)/carboplatin (Carbo) as reference. Subgroup analysis was conducted for elderly patients (≥70 years old). Results The most common five regimens for the eligible patients were as follows: Pac/Carbo (n=3,009), pemetrexed (Pem)/Carbo (n=1,625), Pem/Carbo/bevacizumab (Bev) (n=735), Pac/Carbo/Bev (n=531), Pem/cisplatin (Cis) (n=357), and docetaxel (Doc)/Carbo (n=355). Highest IRs were reported for anemia, neutropenia, nausea, and vomiting across these regimens in patients of all ages. After propensity score stratification, compared with Pac/Carbo, risk of anemia was significantly lower with Pac/Carbo/Bev (HR =0.67), Pem/Cis (HR =0.68), and Pem/Carbo/Bev (HR =0.82); risk of neutropenia was comparable among all regimens except Doc/Carbo (significantly lower risk; HR =0.72); and risk of nausea (HR =1.45) and vomiting (HR =1.50) was significantly higher with Pem/Cis. Safety outcomes in elderly patients were consistent with the overall population. Conclusions While EMR data have limitations, the real-world safety outcome with individual chemotherapy regimen could be considered for the better selection of platinum-based therapies in NSCLC.
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Affiliation(s)
- Lei Chen
- Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA
| | - Jong Seok Kim
- Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA
| | | | - Yajun Emily Zhu
- Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA
| | - Lucy Mitchell
- Eli Lilly and Company, Erl Wood, Windlesham, Surrey, UK
| | - William John
- Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA
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