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Qin Y, Yao S, Huang H, Xiao Y, Wang J, She L, Chen C, Wang X, Luo A, Zhu G. Peripheral eosinophils and immunotherapy response in patients with recurrent or metastatic HNSCC. Sci Rep 2025; 15:17351. [PMID: 40389501 PMCID: PMC12089525 DOI: 10.1038/s41598-025-01457-6] [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: 09/29/2024] [Accepted: 05/06/2025] [Indexed: 05/21/2025] Open
Abstract
This study investigates the relationship between absolute eosinophil count (AEC) and eosinophil percentage (EOS%) with response rates to immune checkpoint inhibitors (ICIs) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. The analysis included data from R/M HNSCC patients treated with ICIs at Second Xiangya Hospital (2016-2021), assessing baseline characteristics, tumor specifics, immune-related adverse events, AEC, and EOS%. The correlation between these factors and ICI response rates was evaluated using logistic regression, while survival outcomes were analyzed through Kaplan-Meier curves and Cox models. Among 74 patients, 59 had low AEC and 15 high, with 53 presenting low EOS% and 21 high. Low AEC (44.07% response rate) and EOS% (47.17%) yielded better responses compared to high levels (40% and 33.33%, respectively). Median overall survival was longer for low AEC (22.63 vs. 18.00 months, P < 0.001) and low EOS% (22.07 vs. 19.73 months, P = 0.02). Both low AEC and EOS% correlated with improved survival odds (3.85 and 2.41 times respectively). Lower AEC and EOS% are independently linked to better survival and increased ICI response rates in R/M HNSCC patients, indicating their potential as predictors for ICI treatment outcomes.
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Affiliation(s)
- Yuexiang Qin
- Department of Health Management Medicine, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan Province, China
- Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
| | - Shanhu Yao
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan Province, China
- Department of Biomedical Informatics, School of Life Sciences, Central South University, Changsha, 410013, Hunan Province, China
- Key Laboratory of Medical Information Research, Central South University, Changsha, 410013, Hunan Province, China
| | - Huimei Huang
- Department of Otolaryngology, Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
| | - Yuyang Xiao
- Department of Health Management Medicine, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan Province, China
| | - Juncheng Wang
- Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
| | - Li She
- Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
| | - Changhan Chen
- Xiangya Hospital, National Medical Metabolomics International Collaborative Research Center, Central South University, Changsha, 410008, Hunan Province, China
| | - Xingwei Wang
- Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China
| | - Aijing Luo
- Key Laboratory of Medical Information Research, Central South University, Changsha, 410013, Hunan Province, China
- The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, China
| | - Gangcai Zhu
- Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China.
- Department of Otolaryngology, Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China.
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2
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Xu Y, Guo Q, Chen Z, Liu Y, Yang Y. Overview of new indications for novel drugs approved in China between 2018 and 2024. Drug Discov Today 2025; 30:104342. [PMID: 40122451 DOI: 10.1016/j.drudis.2025.104342] [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: 10/04/2024] [Revised: 03/07/2025] [Accepted: 03/18/2025] [Indexed: 03/25/2025]
Abstract
Since China's regulatory reforms were initiated in 2015, the development of new indications for novel drugs has become an important trend. Between 2018 and 2024, China's National Medical Products Administration (NMPA) approved 313 new indications for 151 novel drugs. This cross-sectional study comprehensively depicts the landscape of China's new indications for novel drugs, including the characteristics of approvals, quality, and quantity of clinical trial evidence. The quality characteristics of the efficacy evidence for new indications were affected by the treatment areas and conditional approval programs. The efficacy of a novel drug for a new indication can be demonstrated by one pivotal trial or one pivotal trial plus supportive evidence in most cases.
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Affiliation(s)
- Yang Xu
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, China; Key Laboratory of Innovative Drug Research and Evaluation, National Medical Products Administration, Beijing, China.
| | - Qixiang Guo
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, China; Key Laboratory of Innovative Drug Research and Evaluation, National Medical Products Administration, Beijing, China.
| | - Ziqi Chen
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA
| | - Yunpeng Liu
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, China; Key Laboratory of Innovative Drug Research and Evaluation, National Medical Products Administration, Beijing, China; School of Biomedical Engineering, Hainan University, Haikou, China
| | - Yue Yang
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, China; Key Laboratory of Innovative Drug Research and Evaluation, National Medical Products Administration, Beijing, China.
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Mehta A, Motavaf M, Nebo I, Luyten S, Osei-Opare KD, Gru AA. Advancements in Melanoma Treatment: A Review of PD-1 Inhibitors, T-VEC, mRNA Vaccines, and Tumor-Infiltrating Lymphocyte Therapy in an Evolving Landscape of Immunotherapy. J Clin Med 2025; 14:1200. [PMID: 40004731 PMCID: PMC11856346 DOI: 10.3390/jcm14041200] [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: 01/16/2025] [Revised: 02/08/2025] [Accepted: 02/11/2025] [Indexed: 02/27/2025] Open
Abstract
Melanoma, an aggressive skin cancer, presents significant therapeutic challenges. Consequently, innovative treatment strategies beyond conventional chemotherapy, radiation, and surgery are actively explored. This review discusses the evolution of immunotherapy in advanced melanoma, highlighting PD-1/PD-L1 inhibitors, mRNA vaccines, Talimogene Laherparepvec (T-VEC), and tumor-infiltrating lymphocyte (TIL) therapies. PD-1/PD-L1 inhibitors such as pembrolizumab and nivolumab block immune checkpoints, promoting T-cell cytotoxic activity and improving overall survival in patients with advanced melanoma. T-VEC, a modified oncolytic herpes virus, promotes a systemic anti-tumor response while simultaneously lysing malignant cells. mRNA vaccines, such as Moderna's mRNA-4157/V940, take advantage of malignant-cell-specific neoantigens to amplify the adaptive immune response while protecting healthy tissue. TIL therapy is a form of therapy involving ex vivo expansion and reinfusion of the patient's tumor-specific lymphocytes and has been shown to provide durable tumor control. While these therapies have demonstrated promising clinical outcomes, challenges such as tumor resistance, high financial burden, and limited accessibility pose challenges to their widespread use. This review explores combination therapies such as PD-L1 inhibitors with mRNA vaccines, or TIL therapy, which aim to enhance treatment through synergistic approaches. Further research is required to optimize these combinations, address barriers preventing their use, and control adverse events.
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Affiliation(s)
- Apoorva Mehta
- Columbia University Vagelos College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA; (I.N.); (S.L.); (K.D.O.-O.)
| | - Mateen Motavaf
- Duke University School of Medicine, Durham, NC 27710, USA;
| | - Ikenna Nebo
- Columbia University Vagelos College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA; (I.N.); (S.L.); (K.D.O.-O.)
| | - Sophia Luyten
- Columbia University Vagelos College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA; (I.N.); (S.L.); (K.D.O.-O.)
| | - Kofi D. Osei-Opare
- Columbia University Vagelos College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA; (I.N.); (S.L.); (K.D.O.-O.)
| | - Alejandro A. Gru
- Department of Dermatology, Columbia University Irving Medical Center, New York, NY 10032, USA;
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Yi M, Li T, Niu M, Wu Y, Zhao B, Shen Z, Hu S, Zhang C, Zhang X, Zhang J, Yan Y, Zhou P, Chu Q, Dai Z, Wu K. Blockade of CCR5 + T Cell Accumulation in the Tumor Microenvironment Optimizes Anti-TGF-β/PD-L1 Bispecific Antibody. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2408598. [PMID: 39303165 PMCID: PMC11578335 DOI: 10.1002/advs.202408598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 09/11/2024] [Indexed: 09/22/2024]
Abstract
In the previous studies, anti-TGF-β/PD-L1 bispecific antibody YM101 is demonstrated, with superior efficacy to anti-PD-L1 monotherapy in multiple tumor models. However, YM101 therapy can not achieve complete regression in most tumor-bearing mice, suggesting the presence of other immunosuppressive elements in the tumor microenvironment (TME) beyond TGF-β and PD-L1. Thoroughly exploring the TME is imperative to pave the way for the successful translation of anti-TGF-β/PD-L1 BsAb into clinical practice. In this work, scRNA-seq is employed to comprehensively profile the TME changes induced by YM101. The scRNA-seq analysis reveals an increase in immune cell populations associated with antitumor immunity and enhances cell-killing pathways. However, the analysis also uncovers the presence of immunosuppressive CCR5+ T cells in the TME after YM101 treatment. To overcome this hurdle, YM101 is combined with Maraviroc, a widely used CCR5 antagonist for treating HIV infection, suppressing CCR5+ T cell accumulation, and optimizing the immune response. Mechanistically, YM101-induced neutrophil activation recruits immunosuppressive CCR5+ T cells via CCR5 ligand secretion, creating a feedback loop that diminishes the antitumor response. Maraviroc then cleared these infiltrating cells and offset YM101-mediated immunosuppressive effects, further unleashing the antitumor immunity. These findings suggest selectively targeting CCR5 signaling with Maraviroc represents a promising and strategic approach to enhance YM101 efficacy.
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Affiliation(s)
- Ming Yi
- Department of Breast SurgeryThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310000P. R. China
- Cancer CenterShanxi Bethune HospitalShanxi Academy of Medical ScienceTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuan030032P. R. China
| | - Tianye Li
- Department of GynecologyThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou310009P. R. China
| | - Mengke Niu
- Department of Medical OncologyThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310000P. R. China
- Department of OncologyTongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030P. R. China
| | - Yuze Wu
- Department of OncologyTongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030P. R. China
| | - Bin Zhao
- Department of Breast SurgeryThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310000P. R. China
| | - Zhuoyang Shen
- Department of Breast SurgeryThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310000P. R. China
| | - Shengtao Hu
- Department of Breast SurgeryThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310000P. R. China
| | - Chaomei Zhang
- Department of Breast SurgeryThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310000P. R. China
| | - Xiaojun Zhang
- Cancer CenterShanxi Bethune HospitalShanxi Academy of Medical ScienceTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuan030032P. R. China
| | - Jing Zhang
- Wuhan YZY Biopharma Co., LtdBiolake, C2‐1, No.666 Gaoxin RoadWuhan430075P. R. China
| | - Yongxiang Yan
- Wuhan YZY Biopharma Co., LtdBiolake, C2‐1, No.666 Gaoxin RoadWuhan430075P. R. China
| | - Pengfei Zhou
- Wuhan YZY Biopharma Co., LtdBiolake, C2‐1, No.666 Gaoxin RoadWuhan430075P. R. China
| | - Qian Chu
- Department of OncologyTongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030P. R. China
| | - Zhijun Dai
- Department of Breast SurgeryThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310000P. R. China
| | - Kongming Wu
- Cancer CenterShanxi Bethune HospitalShanxi Academy of Medical ScienceTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuan030032P. R. China
- Department of OncologyTongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030P. R. China
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Engel A, Cohen O. Trends in Israeli clinical trials registration "MyTrial". Isr J Health Policy Res 2024; 13:62. [PMID: 39449092 PMCID: PMC11515498 DOI: 10.1186/s13584-024-00643-7] [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: 11/21/2023] [Accepted: 09/23/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND Clinical trial registration is critical for research transparency and integrity. Since 2005, the Declaration of Helsinki has required prospective registration of trials before subject recruitment. In Israel, the MyTrial registry was established in 2015 to register interventional trials and became mandatory in 2016 for ethical approval. The study aimed to analyze the registration practices, challenges, and trends in clinical trial registration in Israel using the local registry "MyTrial". METHODS A total of 3,895 clinical trial records from 2011 to December 2022 were retrieved from the MyTrial platform and subjected to descriptive analysis. RESULTS A significant increase occurred from 2016 to 2021 due to mandated registration, with a peak in 2020 (733 trials) and a decrease in 2022 (462 trials), likely due to COVID-19. Most of the trials included drugs (56%) or medical devices (33%). Geographically, 53% were from central Israel. Only 39% of the patients were registered at both MyTrial and ClinicalTrials.gov. 65% had no blinding. 47% featured unregistered products. 56% had not started recruitment. Since 2016, the number of advanced therapy trials has steadily increased, reaching 19 in 2022. There are gaps between registered trials and official government reports. CONCLUSION These findings provide valuable insights into the current landscape of clinical trial registration in Israel and highlight the need for improvements in compliance with prospective registration and adherence to the WHO-ICTRP standards.
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Affiliation(s)
- Anat Engel
- Health Administration Department Wolfson Medical Center, Holon, Israel
| | - Ornit Cohen
- Research and Innovation Authority, Wolfson Medical Center, Holon, Israel.
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Chen QA, Ma K, Zhang L, Lin WH, Wu XX, Gao YB. Efficacy and Safety of Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Antibodies Plus Chemotherapy as First-Line Treatment for NSCLC in the People's Republic of China: a Systematic Review and Meta-Analysis. JTO Clin Res Rep 2024; 5:100678. [PMID: 38846810 PMCID: PMC11153918 DOI: 10.1016/j.jtocrr.2024.100678] [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: 01/25/2024] [Revised: 04/10/2024] [Accepted: 04/19/2024] [Indexed: 06/09/2024] Open
Abstract
Introduction The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.
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Affiliation(s)
- Qi-An Chen
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Kai Ma
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People’s Republic of China
| | - Lin Zhang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People’s Republic of China
| | - Wei-Hao Lin
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
| | - Xian-Xian Wu
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People’s Republic of China
| | - Yi-Bo Gao
- Central Laboratory & Shenzhen Key Laboratory of Epigenetics and Precision Medicine for Cancers, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, People’s Republic of China
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
- Laboratory of Translational Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
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7
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Wang DX, Liu H, Tian JC, Zhang DL, Yan LJ, Ding ZN, Li H, Yan YC, Dong ZR, Li T. Neoadjuvant immunotherapy based on PD-1/L1 inhibitors for gastrointestinal tumors: a review of the rationale and clinical advances. Int J Surg 2024; 110:3707-3722. [PMID: 38518083 PMCID: PMC11175801 DOI: 10.1097/js9.0000000000001357] [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: 10/25/2023] [Accepted: 03/03/2024] [Indexed: 03/24/2024]
Abstract
The landscape of current tumor treatment has been revolutionized by the advent of immunotherapy based on PD-1/PD-L1 inhibitors. Leveraging its capacity to mobilize systemic antitumor immunity, which is primarily mediated by T cells, there is growing exploration and expansion of its potential value in various stages of clinical tumor treatment. Neoadjuvant immunotherapy induces a robust immune response against tumors prior to surgery, effectively facilitating tumor volume reduction, early eradication or suppression of tumor cell activity, and control of potential metastatic spread, to improve curative surgical resection rates, and prevent tumor recurrence. This review delineates the theoretical basis of neoadjuvant immunotherapy from preclinical research evidence, discusses specific challenges in clinical application, and provides a comprehensive overview of clinical research progress in neoadjuvant immunotherapy for gastrointestinal tumors. These findings suggest that neoadjuvant immunotherapy has the potential to ameliorate immunosuppressive states and enhance cytotoxic T cell function while preserving lymphatic drainage in the preoperative period. However, further investigations are needed on specific treatment regimens, suitable patient populations, and measurable endpoints. Despite numerous studies demonstrating the promising efficacy and manageable adverse events of neoadjuvant immunotherapy in gastrointestinal tumors, the availability of high-quality randomized controlled trials is limited, which highlights the necessity for further research.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Tao Li
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, People’s Republic of China
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Kammula AV, Schäffer AA, Rajagopal PS, Kurzrock R, Ruppin E. Outcome differences by sex in oncology clinical trials. Nat Commun 2024; 15:2608. [PMID: 38521835 PMCID: PMC10960820 DOI: 10.1038/s41467-024-46945-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 03/15/2024] [Indexed: 03/25/2024] Open
Abstract
Identifying sex differences in outcomes and toxicity between males and females in oncology clinical trials is important and has also been mandated by National Institutes of Health policies. Here we analyze the Trialtrove database, finding that, strikingly, only 472/89,221 oncology clinical trials (0.5%) had curated post-treatment sex comparisons. Among 288 trials with comparisons of survival, outcome, or response, 16% report males having statistically significant better survival outcome or response, while 42% reported significantly better survival outcome or response for females. The strongest differences are in trials of EGFR inhibitors in lung cancer and rituximab in non-Hodgkin's lymphoma (both favoring females). Among 44 trials with side effect comparisons, more trials report significantly lesser side effects in males (N = 22) than in females (N = 13). Thus, while statistical comparisons between sexes in oncology trials are rarely reported, important differences in outcome and toxicity exist. These considerable outcome and toxicity differences highlight the need for reporting sex differences more thoroughly going forward.
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Affiliation(s)
- Ashwin V Kammula
- Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA
| | - Alejandro A Schäffer
- Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
| | - Padma Sheila Rajagopal
- Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA
- Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA
| | - Razelle Kurzrock
- WIN Consortium and Medical College of Wisconsin, Milwaukee, WI 53226 and University of Nebraska, Omaha, NE, 68198, USA
| | - Eytan Ruppin
- Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
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9
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Schäffer AA, Chung Y, Kammula AV, Ruppin E, Lee JS. A systematic analysis of the landscape of synthetic lethality-driven precision oncology. MED 2024; 5:73-89.e9. [PMID: 38218178 DOI: 10.1016/j.medj.2023.12.009] [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: 07/07/2023] [Revised: 09/10/2023] [Accepted: 12/13/2023] [Indexed: 01/15/2024]
Abstract
BACKGROUND Synthetic lethality (SL) denotes a genetic interaction between two genes whose co-inactivation is detrimental to cells. Because more than 25 years have passed since SL was proposed as a promising way to selectively target cancer vulnerabilities, it is timely to comprehensively assess its impact so far and discuss its future. METHODS We systematically analyzed the literature and clinical trial data from the PubMed and Trialtrove databases to portray the preclinical and clinical landscape of SL oncology. FINDINGS We identified 235 preclinically validated SL pairs and found 1,207 pertinent clinical trials, and the number keeps increasing over time. About one-third of these SL clinical trials go beyond the typically studied DNA damage response (DDR) pathway, testifying to the recently broadening scope of SL applications in clinical oncology. We find that SL oncology trials have a greater success rate than non-SL-based trials. However, about 75% of the preclinically validated SL interactions have not yet been tested in clinical trials. CONCLUSIONS Dissecting the recent efforts harnessing SL to identify predictive biomarkers, novel therapeutic targets, and effective combination therapy, our systematic analysis reinforces the hope that SL may serve as a key driver of precision oncology going forward. FUNDING Funded by the Samsung Research Funding & Incubation Center of Samsung Electronics, the Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by the Republic of Korea government (MSIT), the Kwanjeong Educational Foundation, the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), and Center for Cancer Research (CCR).
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Affiliation(s)
- Alejandro A Schäffer
- Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
| | - Youngmin Chung
- Department of Artificial Intelligence, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Ashwin V Kammula
- Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
| | - Eytan Ruppin
- Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
| | - Joo Sang Lee
- Department of Artificial Intelligence, Sungkyunkwan University, Suwon 16419, Republic of Korea; Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Republic of Korea; Department of Digital Health & Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Samsung Medical Center, Sungkyunkwan University, Seoul 06351, Republic of Korea.
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10
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Cascone T, Kar G, Spicer JD, García-Campelo R, Weder W, Daniel DB, Spigel DR, Hussein M, Mazieres J, Oliveira J, Yau EH, Spira AI, Anagnostou V, Mager R, Hamid O, Cheng LY, Zheng Y, Blando J, Tan TH, Surace M, Rodriguez-Canales J, Gopalakrishnan V, Sellman BR, Grenga I, Soo-Hoo Y, Kumar R, McGrath L, Forde PM. Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial. Cancer Discov 2023; 13:2394-2411. [PMID: 37707791 PMCID: PMC10618740 DOI: 10.1158/2159-8290.cd-23-0436] [Citation(s) in RCA: 61] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 07/14/2023] [Accepted: 08/31/2023] [Indexed: 09/15/2023]
Abstract
Neoadjuvant chemoimmunotherapy improves pathologic complete response rate and event-free survival in patients with resectable non-small cell lung cancer (NSCLC) versus chemotherapy alone. NeoCOAST was the first randomized, multidrug platform trial to examine novel neoadjuvant immuno-oncology combinations for patients with resectable NSCLC, using major pathologic response (MPR) rate as the primary endpoint. Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti-PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). MPR rates were higher for patients in the combination arms versus durvalumab alone. Safety profiles for the combinations were similar to those of durvalumab alone. Multiplatform immune profiling suggested that improved MPR rates in the durvalumab plus oleclumab and durvalumab plus monalizumab arms were associated with enhanced effector immune infiltration of tumors, interferon responses and markers of tertiary lymphoid structure formation, and systemic functional immune cell activation. SIGNIFICANCE A neoadjuvant platform trial can rapidly generate clinical and translational data using candidate surrogate endpoints like MPR. In NeoCOAST, patients with resectable NSCLC had improved MPR rates after durvalumab plus oleclumab or monalizumab versus durvalumab alone and tumoral transcriptomic signatures indicative of augmented immune cell activation and function. See related commentary by Cooper and Yu, p. 2306. This article is featured in Selected Articles from This Issue, p. 2293.
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Affiliation(s)
- Tina Cascone
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Gozde Kar
- AstraZeneca, Translational Medicine, Research and Early Development, Oncology Research and Development, Cambridge, United Kingdom
| | - Jonathan D. Spicer
- Department of Thoracic Surgery, McGill University, Montreal, Quebec, Canada
| | | | - Walter Weder
- Thoracic Surgery, Clinic Bethanien, Zurich, Switzerland
| | - Davey B. Daniel
- Sarah Cannon Research Institute/Tennessee Oncology, Nashville, Tennessee
| | - David R. Spigel
- Sarah Cannon Research Institute/Tennessee Oncology, Nashville, Tennessee
| | - Maen Hussein
- Sarah Cannon Research Institute, Florida Cancer Specialists, Leesburg, Florida
| | - Julien Mazieres
- Thoracic Oncology Department, Toulouse University Hospital, Toulouse, France
| | - Julio Oliveira
- Medical Oncology Department, Portuguese Oncology Institute (IPO-PORTO), Porto, Portugal
| | - Edwin H. Yau
- Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Alexander I. Spira
- Virginia Cancer Specialists, US Oncology Research, NEXT Oncology Virginia, Fairfax, Virginia
| | - Valsamo Anagnostou
- Bloomberg–Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Patrick M. Forde
- Bloomberg–Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
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11
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Liang H, Lu Q, Yang J, Yu G. Supramolecular Biomaterials for Cancer Immunotherapy. RESEARCH (WASHINGTON, D.C.) 2023; 6:0211. [PMID: 37705962 PMCID: PMC10496790 DOI: 10.34133/research.0211] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 08/01/2023] [Indexed: 09/15/2023]
Abstract
Cancer immunotherapy has achieved tremendous successful clinical results and obtained historic victories in tumor treatments. However, great limitations associated with feeble immune responses and serious adverse effects still cannot be neglected due to the complicated multifactorial etiology and pathologic microenvironment in tumors. The rapid development of nanomedical science and material science has facilitated the advanced progress of engineering biomaterials to tackle critical issues. The supramolecular biomaterials with flexible and modular structures have exhibited unparalleled advantages of high cargo-loading efficiency, excellent biocompatibility, and diversiform immunomodulatory activity, thereby providing a powerful weapon for cancer immunotherapy. In past decades, supramolecular biomaterials were extensively explored as versatile delivery platforms for immunotherapeutic agents or designed to interact with the key moleculars in immune system in a precise and controllable manner. In this review, we focused on the crucial role of supramolecular biomaterials in the modulation of pivotal steps during tumor immunotherapy, including antigen delivery and presentation, T lymphocyte activation, tumor-associated macrophage elimination and repolarization, and myeloid-derived suppressor cell depletion. Based on extensive research, we explored the current limitations and development prospects of supramolecular biomaterials in cancer immunotherapy.
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Affiliation(s)
- Huan Liang
- College of Science,
Nanjing Forestry University, Nanjing 210037, P. R. China
| | - Qingqing Lu
- College of Science,
Nanjing Forestry University, Nanjing 210037, P. R. China
| | - Jie Yang
- College of Science,
Nanjing Forestry University, Nanjing 210037, P. R. China
| | - Guocan Yu
- Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry,
Tsinghua University, Beijing 100084, P. R. China
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12
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Wu D, Hu L, Wang X, Yu Y, Jia SP, Huang HY, Li ZW, Ma JF, Zhu HB, Tang Y, Li N. Clinical development of mRNA therapies against solid tumors. J Hematol Oncol 2023; 16:75. [PMID: 37464375 PMCID: PMC10354897 DOI: 10.1186/s13045-023-01457-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 05/18/2023] [Indexed: 07/20/2023] Open
Abstract
The mRNA-based therapeutics have become the hot spot of biopharmaceutical industries in recent years. The landscape of this area is expanding from infectious disease to cancer, which needs to be summarized to provide data supports for industries and research institutions. Based on the Trialtrove database, a total of 108 clinical trials from 1999 to 2021 were retrospectively analyzed. We have demonstrated that the clinical development of mRNA therapies against solid tumors is still at an early stage. There are evolutions in delivery systems from the dendritic cell to the lipid-based platform and in encoding strategies from the fixed tumor antigens to the personalized neoantigens. The adjuvant or maintenance therapy and the combination treatment with checkpoint inhibitors are becoming the major clinical development orientation.
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Affiliation(s)
- Dawei Wu
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lingfeng Hu
- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
| | - Xin Wang
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Clinical Trials Center, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Yue Yu
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuo-Peng Jia
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang, China
| | - Hui-Yao Huang
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zi-Wei Li
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Jin-Feng Ma
- Department of Clinical Trials Center, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Hai-Bo Zhu
- Department of Clinical Trials Center, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Yu Tang
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ning Li
- Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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13
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Bay JO, Bouleuc C, Caux C, Delom F, Firmin N, Gandemer V, L'Allemain G, Magné N, Orbach D, Robert J, Rodrigues M, Sabatier R, Thiery-Vuillemin A, Wislez M. [A 2022 inventory in oncology news]. Bull Cancer 2023; 110:19-31. [PMID: 36529541 DOI: 10.1016/j.bulcan.2022.12.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 12/23/2022]
Abstract
The Cancer Bulletin continues its tradition. At the beginning of 2023, the members of the editorial committee would like to share with you their analyses of the highlights of 2022. The objective remains to highlight what will change our practices and lead to different diagnostic or therapeutic options. Our synthesis will therefore focus on published data. They have been analyzed and placed in the more general context of the management of each type of cancer to deduce the practical consequences for our patients. This synthesis exercise will concern almost all tumor pathologies, most often on the therapeutic level, and will, however, exclude the evolution of techniques, whether they are diagnostic or used for the follow-up of our patients. The final objective is to allow you to have a thoughtful, didactic and practical reading. Our goal is to provide our readers with the rational bases that can lead to a different approach for treatments in 2023.
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Affiliation(s)
- Jacques-Olivier Bay
- CHU de Clermont-Ferrand, service de thérapie cellulaire et d'hématologie clinique adulte, UE7453 CHELTER, Inserm CIC-501, site Estaing, 63000 Clermont-Ferrand, France.
| | - Carole Bouleuc
- Sorbonne université, Paris, France; Institut Curie, département de soins de support, 26, rue d'Ulm, 75005 Paris, France
| | - Christophe Caux
- Université Claude-Bernard Lyon 1, CNRS 5286, centre de recherche en cancérologie de Lyon, Inserm U1052, 69008 Lyon, France
| | - Frédéric Delom
- University Bordeaux, ARTiSt Lab, Inserm U1312, 33000 Bordeaux, France
| | - Nelly Firmin
- Université Montpellier, ICM Montpellier, IRCM, Inserm U1194, 208, avenue des apothicaires, 34298 Montpellier, France
| | - Virginie Gandemer
- CHU de Rennes, service d'hémato-oncologie pédiatrique, 35000 ReDnnes, France
| | - Gilles L'Allemain
- Université Côte d'Azur, CNRS, Inserm, institut biologie Valrose, 06108 Nice, France
| | - Nicolas Magné
- Institut Bergonie, département de radiothérapie, Bordeaux, France
| | - Daniel Orbach
- PSL université, institut Curie, centre intégré de soins et de recherche en oncologie de l'enfant, adolescent et jeune adulte (SIREDO), 26, rue d'Ulm, 75005 Paris, France
| | - Jacques Robert
- Université de Bordeaux, Inserm U1218, 33000 Bordeaux, France
| | - Manuel Rodrigues
- PSL Research University, institut Curie, département d'oncologie médicale, 26, rue d'Ulm, 75005 Paris, France
| | - Renaud Sabatier
- Aix-Marseille université, CNRS, institut Paoli-Calmettes, département d'oncologie médicale, Inserm, Marseille, France
| | - Antoine Thiery-Vuillemin
- CHRU Jean-Minjoz, department of medical oncology, 25030 Besançon cedex, France; Université de Franche-Comté, SFR IBCT, Inserm U1098, 25020 Besançon cedex, France
| | - Marie Wislez
- AP-HP Centre, hôpital Cochin, service de pneumologie, unité d'oncologie thoracique, 75000 Paris, France
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Abstract
IMPORTANCE The recent successes of poly-ADP ribose polymerase (PARP) inhibitors and belzutifan support germline genetic data as an exciting, accessible source for biomarkers in cancer treatment. This study hypothesizes, however, that most oncology clinical trials using germline data largely prioritize BRCA1/2 as biomarkers and PARP inhibitors as therapy. OBJECTIVE To characterize past and ongoing oncology trials that use germline data. DESIGN, SETTING, AND PARTICIPANTS This retrospective cross-sectional study of oncology trials used the Informa Trialtrove database to evaluate trial attributes. Trials using germline information (including the terms germline, hereditary, or inherited in the title, treatment plan, interventions, end points, objectives, results, or notes) and conducted globally between December 1, 1990, and April 4, 2022 (data freeze date), were included. MAIN OUTCOMES AND MEASURES Trials by cancer type, phase, participants, sponsor type, end points, outcomes, and locations were described. Associated biomarkers and mechanisms of action for studied therapeutic interventions were counted. How germline data in trial inclusion and exclusion criteria are associated with end points, outcomes, and enrollment were also examined. RESULTS A total of 887 of 84 297 (1.1%) oncology clinical trials in the Trialtrove database that use germline data were identified. Most trials were conducted in cancer types where PARP inhibitors are already approved. A total of 74.8% (672) of trials were performed in the phase 2 setting or above. Trials were primarily sponsored by industry (523 trials [59.0%]), academia (382 trials [43.1%]), and the government (274 trials [30.9%]), where trials may have multiple sponsor types. Among 343 trials using germline data with outcomes in Trialtrove, 180 (52.5%) reported meeting primary end points. Although BRCA1/2 are the most frequent biomarkers seen (BRCA1, 224 trials [25.3%]; BRCA2, 228 trials [25.7%]), trials also examine pharmacogenomic variants and germline mediators of somatic biomarkers. PARP inhibitors or immunotherapy were tested in 69.9% of trials; PARP inhibition was the most frequently studied mechanism (367 trials [41.4%]). An overwhelming number of trials using germline data were conducted in the US, Canada, and Europe vs other countries, mirroring disparities in cancer genetics data. Germline data in inclusion and exclusion criteria are associated with altered end point, outcomes, and enrollment compared with oncology trials with no germline data use. Examples of inclusion and exclusion criteria regarding germline data that may unintentionally exclude patients were identified. CONCLUSIONS AND RELEVANCE These findings suggest that for germline biomarkers to gain clinical relevance, trials must expand biomarkers, therapies, and populations under study.
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Affiliation(s)
- Ashwin V Kammula
- Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
- University of Maryland, College Park
| | - Alejandro A Schäffer
- Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
| | - Padma Sheila Rajagopal
- Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
- Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
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15
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黄 慧, 刘 梅, 李 喜, 孟 鑫, 崔 丹, 冷 烨, 唐 玉, 李 宁. [Progress and Application of Bayesian Approach in the Early Research and Development of New Anticancer Drugs]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2022; 25:730-734. [PMID: 36285392 PMCID: PMC9619348 DOI: 10.3779/j.issn.1009-3419.2022.102.43] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/17/2022] [Accepted: 09/26/2022] [Indexed: 12/02/2022]
Abstract
Bayesian statistics is an approach for learning from evidences as it accumulates, combining prior distribution with current information on a quantity of interest, in which posterior distribution and inferences are being updated each time new data become available using Bayes' Theorem. Though frequentist approach has dominated medical studies, Bayesian approach has been more and more widely recognized by its flexibility and efficiency. Research and development (R&D) on anti-cancer new drugs have been so hot globally in recent years in spite of relatively high failure rate. It is the common demand of pharmaceutical enterprises and researchers to identify the optimal dose, regime and right population in the early-phase R&D stage more accurately and efficiently, especially when the following three major changes have been observed. The R&D on anticancer drugs have transformed from chemical drugs to biological products, from monotherapy to combination therapy, and the study design has also gradually changed from traditional way to innovative and adaptive mode. This also raises a number of subsequent challenges on decision-making of early R&D, such as inability to determine MTD, flexibility to deal with delayed toxicity, delayed response and dose-response changing relationships. It is because of the above emerging changes and challenges that the Bayesian approach is getting more and more attention from the industry. At least, Bayesian approach has more information for decision-making, which could potentially help enterprises achieve higher efficiency, shorter period and lower investment. This study also expounds the application of Bayesian statistics in the early R&D on anticancer new drugs, and compares and analyzes its idea and application scenarios with frequentist statistics, aiming to provide macroscopic and systematic reference for all related stakeholders.
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Affiliation(s)
- 慧瑶 黄
- 100021 北京,国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院,药物临床试验研究中心Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- 065001 廊坊,国家癌症中心/国家肿瘤临床医学研究中心/河北中国医学科学院肿瘤医院,药物临床试验研究中心Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang 065001, China
| | - 梅若 刘
- 201203 上海,勃林格殷格翰(中国)投资有限公司数据分析与统计部门Department of Biostatistics and Data Sciences, Boehringer Ingelheim (China) Investment Co Ltd, Shanghai 201203, China
| | - 喜艳 李
- 201203 上海,勃林格殷格翰(中国)投资有限公司数据分析与统计部门Department of Biostatistics and Data Sciences, Boehringer Ingelheim (China) Investment Co Ltd, Shanghai 201203, China
| | - 鑫雨 孟
- 3010 维多利亚州,墨尔本大学公共卫生学院School of Population and Global Health, the University of Melbourne, Victoria 3010, Australia
| | - 丹丹 崔
- 065001 廊坊,国家癌症中心/国家肿瘤临床医学研究中心/河北中国医学科学院肿瘤医院,药物临床试验研究中心Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang 065001, China
| | - 烨 冷
- 211198 南京,中国药科大学基础医学与临床药学系School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China
| | - 玉 唐
- 100021 北京,国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院,药物临床试验研究中心Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- 065001 廊坊,国家癌症中心/国家肿瘤临床医学研究中心/河北中国医学科学院肿瘤医院,药物临床试验研究中心Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang 065001, China
| | - 宁 李
- 100021 北京,国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院,药物临床试验研究中心Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- 065001 廊坊,国家癌症中心/国家肿瘤临床医学研究中心/河北中国医学科学院肿瘤医院,药物临床试验研究中心Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang 065001, China
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16
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Huang H, Zhu Q, Ga M, Wu D, Meng X, Wang S, Fang H, Tang Y, Li N. Availability and Affordability of Oncology Drugs in 2012-2021 in China and the United States. Front Oncol 2022; 12:930846. [PMID: 35936746 PMCID: PMC9355250 DOI: 10.3389/fonc.2022.930846] [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: 04/28/2022] [Accepted: 06/20/2022] [Indexed: 12/04/2022] Open
Abstract
OBJECTIVE To systematically summarize the landscape and characteristics of all approved new anticancer drugs for the last 10 years in China and the United States (US) to further inform the trend, current state, and existing gap in the availability and affordability of cancer medicine between the two countries. METHODS Mainly based on the Pharmcube database, a list and detailed information of anticancer drugs approved in China and the United States were acquired. The annual number, time lag, and basic characteristics, including drug type, mechanism, enterprise type, indication population, drug target, and cancer type of approved drugs were compared. RESULTS Eighty-seven and 118 new anticancer drugs were approved in China and the US, respectively, showing a stable trend in the US, while a significant increase was observed after 2016 in China. Of the 42 cancer medicines launched in both countries, the US took precedence, and the median time lag markedly decreased, from 6.53 years in 2012 to 0.88 years in 2020. A total of 14.4% of drugs were applicable to children in the US, while only 2.3% were applicable in China, and there was no difference in drug type and enterprise. Thirty-one and 43 targets were explored, with respect to 27 and 36 cancer types in China and the US, respectively, during the period. In addition, the expenditure of drugs on PD-1 and PD-L1 in China was generally lower than that in America. CONCLUSION The availability of new anticancer drugs has increased dramatically in the past decade, particularly in China. Compared with the US, the launch of new anticancer drugs in China lags behind, but the time lag has been shortened significantly, and better affordability is observed in immune drugs. More attention should be given to differentiated innovation, and unmet medical needs in special populations like childhood tumors, which are important directions of new drug R&D in China.
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Affiliation(s)
- Huiyao Huang
- Department of Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qi Zhu
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Man Ga
- Department of Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dawei Wu
- Department of Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinyu Meng
- Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC, Australia
| | - Shuhang Wang
- Department of Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Fang
- Department of Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yu Tang
- Department of Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ning Li
- Department of Clinical Trials Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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