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Guan H, Wang C, Chen C, Han S, Zhao Z. Cost-Effectiveness of 12 First-Line Treatments for Patients With Advanced EGFR Mutated NSCLC in the United Kingdom and China. Front Oncol 2022; 12:819674. [PMID: 35785198 PMCID: PMC9241581 DOI: 10.3389/fonc.2022.819674] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 04/22/2022] [Indexed: 12/04/2022] Open
Abstract
Background Lung cancer is imposing significant pressure on the national health insurance system worldwide, especially under the COVID-19 pandemic. However, the cost-effectiveness of all available first-line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) is still uncertain. The aim of this study was to evaluate the cost-effectiveness of 12 first-line treatments for patients with advanced EGFR mutated NSCLC from the perspective of the United Kingdom (UK) National Health Service and Chinese health care system. Methods We used a Markov model to estimate the cost-effectiveness of 12 treatments, including 6 EGFR tyrosine kinase inhibitors, 4 combination treatments and 2 chemotherapies. The key clinical efficacy and safety data were from a network meta-analysis. The cost and health preference were mainly collected from the literature. The most cost-effective treatment was inferred through a sequential analysis. Uncertainty was tested with one-way sensitivity analyses, scenario analyses, and probabilistic sensitivity analyses. Quality-adjusted life years (QALYs), direct medical costs, and incremental cost-effectiveness ratio (ICER) were estimated, at willingness-to-pay thresholds of £20000 to £50000 and £8000 to £24000 per QALY in the UK and China respectively. Results For clinical effectiveness, osimertinib and gefitinib plus pemetrexed based chemotherapy (PbCT) yielded the highest QALYs, while two chemotherapy treatments gained the lowest QALYs. For costs, gefitinib treatment was the cheapest option in both countries (£24529 in the UK and £12961 in China). For cost-effectiveness, 4 treatments including gefitinib, gefitinib plus pemetrexed, gefitinib plus PbCT, and osimertinib formed the cost-effectiveness frontier in both countries. Gefitinib alone (70.7% and 80.0% under the threshold of £20000 and £8000 per QALY in the UK and China, respectively) and gefitinib plus PbCT (62.3% and 71.2% under the threshold of £50000 and £24000 per QALY in the UK and China, respectively) were most likely to be cost-effective compared with other first-line treatments. Conclusions Gefitinib and gefitinib plus PbCT were likely to be cost-effective for patients with advanced EGFR mutated NSCLC in both countries.
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Affiliation(s)
- Haijing Guan
- Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China Center for Health Economic Research, Peking University, Beijing, China
| | - Chunping Wang
- International Research Center for Medicinal Administration, Peking University, Beijing, China
| | - Chen Chen
- China Center for Health Economic Research, Peking University, Beijing, China
- Department of Global Health, School of Public Health, Wuhan University, Wuhan, China
| | - Sheng Han
- International Research Center for Medicinal Administration, Peking University, Beijing, China
| | - Zhigang Zhao
- Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
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Nardone V, Giannicola R, Bianco G, Giannarelli D, Tini P, Pastina P, Falzea AC, Macheda S, Caraglia M, Luce A, Zappavigna S, Mutti L, Pirtoli L, Giordano A, Correale P. Inflammatory Markers and Procalcitonin Predict the Outcome of Metastatic Non-Small-Cell-Lung-Cancer Patients Receiving PD-1/PD-L1 Immune-Checkpoint Blockade. Front Oncol 2021; 11:684110. [PMID: 34195086 PMCID: PMC8236817 DOI: 10.3389/fonc.2021.684110] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 05/24/2021] [Indexed: 12/14/2022] Open
Abstract
Peripheral-immune-checkpoint blockade (P-ICB) with mAbs to PD-1 (nivolumab and pembrolizumab) or PD-L1 (atezolizumab, durvalumab, avelumab) alone or combination with chemotherapy represents a novel active treatment for mNSCLC patients. However, this therapy can be associated to immune-related adverse events (irAEs) and high cost. Therefore, finding reliable biomarkers of response and irAEs is strongly encouraged to accurately select patients who may potentially benefit from the immuno-oncological treatment. This is a retrospective multi-institutional analysis performed on ninety-five mNSCLC patients who received real-world salvage therapy with nivolumab or atezolizumab between December 2015 and April 2020. The outcome of these patients in term of PFS and OS was evaluated in comparison with different serum levels of C-reactive protein (CRP), Erythrocyte Sedimention Rate (ESR) and Procalcitonin (PCT) by performing Kaplan-Meier and Log-rank test and multivariate analysis. We found that high baseline levels of CRP, ESR, and PCT were strongly predictive of poor outcome (P <0.05) with the worse prognosis detected in those patients with a baseline levels of both ESR and PCT over the pre-established cut off (median OS recorded in patients with no marker over the cut off vs. those with just one marker over the cut off vs. those with both markers over the cut off: 40 ± 59 vs. 15.5 ± 5.5 vs. 5.5 ± 1.6 months, respectively; P <0.0001). Our results suggest the predictive value of systemic inflammation and suggest a potential role of PCT in predicting a poor outcome in mNSCLC receiving PD-1/PD-L1 blocking mAbs. This finding also suggests a potential role of subclinical bacterial infections in defining the response to PD-1/PD-L1 blocking mAbs that deserves further and more specific investigations.
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Affiliation(s)
- Valerio Nardone
- Unit of Radiation Oncology, Ospedale del Mare, Naples, Italy
| | - Rocco Giannicola
- Medical Oncology Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy
| | - Giovanna Bianco
- Medical Oncology Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy
| | - Diana Giannarelli
- Biostatistical Unit, National Cancer Institute "Regina Elena", IRCCS, Rome, Italy
| | - Paolo Tini
- Section of Radiation Oncology, Medical School, University of Siena, Siena, Italy
| | - Pierpaolo Pastina
- Section of Radiation Oncology, Medical School, University of Siena, Siena, Italy
| | - Antonia Consuelo Falzea
- Medical Oncology Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy
| | - Sebastiano Macheda
- Unit of Intensive Care Medicine and Anesthesia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio Calabria, Italy
| | - Michele Caraglia
- Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy.,Laboratory of Precision and Molecular Oncology, Institute of Genetic Research, Biogem Scarl, Ariano Irpino, Italy
| | - Amalia Luce
- Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Silvia Zappavigna
- Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Luciano Mutti
- Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, United States
| | - Luigi Pirtoli
- Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, United States
| | - Antonio Giordano
- Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, United States.,Department of Medical Biotechnology, University of Siena, Siena, Italy
| | - Pierpaolo Correale
- Medical Oncology Unit, Grand Metropolitan Hospital "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy.,Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, United States
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Greenhalgh J, Boland A, Bates V, Vecchio F, Dundar Y, Chaplin M, Green JA. First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer. Cochrane Database Syst Rev 2021; 3:CD010383. [PMID: 33734432 PMCID: PMC8092455 DOI: 10.1002/14651858.cd010383.pub3] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Epidermal growth factor receptor (EGFR) mutation positive (M+) non-small cell lung cancer (NSCLC) is an important subtype of lung cancer comprising 10% to 15% of non-squamous tumours. This subtype is more common in women than men, is less associated with smoking, but occurs at a younger age than sporadic tumours. OBJECTIVES To assess the clinical effectiveness of single-agent or combination EGFR therapies used in the first-line treatment of people with locally advanced or metastatic EGFR M+ NSCLC compared with other cytotoxic chemotherapy (CTX) agents used alone or in combination, or best supportive care (BSC). The primary outcomes were overall survival and progression-free survival. Secondary outcomes included response rate, symptom palliation, toxicity, and health-related quality of life. SEARCH METHODS We conducted electronic searches of the Cochrane Register of Controlled Trials (CENTRAL) (2020, Issue 7), MEDLINE (1946 to 27th July 2020), Embase (1980 to 27th July 2020), and ISI Web of Science (1899 to 27th July 2020). We also searched the conference abstracts of the American Society for Clinical Oncology and the European Society for Medical Oncology (July 2020); Evidence Review Group submissions to the National Institute for Health and Care Excellence; and the reference lists of retrieved articles. SELECTION CRITERIA Parallel-group randomised controlled trials comparing EGFR-targeted agents (alone or in combination with cytotoxic agents or BSC) with cytotoxic chemotherapy (single or doublet) or BSC in chemotherapy-naive patients with locally advanced or metastatic (stage IIIB or IV) EGFR M+ NSCLC unsuitable for treatment with curative intent. DATA COLLECTION AND ANALYSIS Two review authors independently identified articles, extracted data, and carried out the 'Risk of bias' assessment. We conducted meta-analyses using a fixed-effect model unless there was substantial heterogeneity, in which case we also performed a random-effects analysis as a sensitivity analysis. MAIN RESULTS Twenty-two trials met the inclusion criteria. Ten of these exclusively recruited people with EGFR M+ NSCLC; the remainder recruited a mixed population and reported results for people with EGFR M+ NSCLC as subgroup analyses. The number of participants with EGFR M+ tumours totalled 3023, of whom approximately 2563 were of Asian origin. Overall survival (OS) data showed inconsistent results between the included trials that compared EGFR-targeted treatments against cytotoxic chemotherapy or placebo. Erlotinib was used in eight trials, gefitinib in nine trials, afatinib in two trials, cetuximab in two trials, and icotinib in one trial. The findings of FASTACT 2 suggested a clinical benefit for OS for participants treated with erlotinib plus cytotoxic chemotherapy when compared to cytotoxic chemotherapy alone, as did the Han 2017 trial for gefitinib plus cytotoxic chemotherapy, but both results were based on a small number of participants (n = 97 and 122, respectively). For progression-free survival (PFS), a pooled analysis of four trials showed evidence of clinical benefit for erlotinib compared with cytotoxic chemotherapy (hazard ratio (HR) 0.31; 95% confidence interval (CI) 0.25 to 0.39 ; 583 participants ; high-certainty evidence). A pooled analysis of two trials of gefitinib versus paclitaxel plus carboplatin showed evidence of clinical benefit for PFS for gefitinib (HR 0.39; 95% CI 0.32 to 0.48 ; 491 participants high-certainty evidence), and a pooled analysis of two trials of gefitinib versus pemetrexed plus carboplatin with pemetrexed maintenance also showed evidence of clinical benefit for PFS for gefitinib (HR 0.59; 95% CI 0.46 to 0.74, 371 participants ; moderate-certainty evidence). Afatinib showed evidence of clinical benefit for PFS when compared with chemotherapy in a pooled analysis of two trials (HR 0.42; 95% CI 0.34 to 0.53, 709 participants high-certainty evidence). All but one small trial showed a corresponding improvement in response rate with tyrosine-kinase inhibitor (TKI) compared to chemotherapy. Commonly reported grade 3/4 adverse events associated with afatinib, erlotinib, gefitinib and icotinib monotherapy were rash and diarrhoea. Myelosuppression was consistently worse in the chemotherapy arms; fatigue and anorexia were also associated with some chemotherapies. Seven trials reported on health-related quality of life and symptom improvement using different methodologies. For each of erlotinib, gefitinib, and afatinib, two trials showed improvement in one or more indices for the TKI compared to chemotherapy. The quality of evidence was high for the comparisons of erlotinib and gefitinib with cytotoxic chemotherapy and for the comparison of afatinib with cytotoxic chemotherapy. AUTHORS' CONCLUSIONS Erlotinib, gefitinib, afatinib and icotinib are all active agents in EGFR M+ NSCLC patients, and demonstrate an increased tumour response rate and prolonged PFS compared to cytotoxic chemotherapy. We found a beneficial effect of the TKI compared to cytotoxic chemotherapy in adverse effect and health-related quality of life. We found limited evidence for increased OS for the TKI when compared with standard chemotherapy, but the majority of the included trials allowed participants to switch treatments on disease progression, which will have a confounding effect on any OS analysis. Single agent-TKI remains the standard of care and the benefit of combining a TKI and chemotherapy remains uncertain as the evidence is based on small patient numbers. Cytotoxic chemotherapy is less effective in EGFR M+ NSCLC than erlotinib, gefitinib, afatinib or icotinib and is associated with greater toxicity. There are no data supporting the use of monoclonal antibody therapy. Icotinib is not available outside China.
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Affiliation(s)
- Janette Greenhalgh
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Angela Boland
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Victoria Bates
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Fabio Vecchio
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Yenal Dundar
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
- Central Queensland Hospital and Health Service, Rockhampton, Australia
| | - Marty Chaplin
- Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
| | - John A Green
- Institute of Translational Medicine, University of Liverpool, Bebington, UK
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Jin J, Robeson H, Fagan P, Orloff MS. Association of PARP1-specific polymorphisms and haplotypes with non-small cell lung cancer subtypes. PLoS One 2020; 15:e0243509. [PMID: 33284833 PMCID: PMC7721167 DOI: 10.1371/journal.pone.0243509] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 11/20/2020] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE The carcinogenesis role of PARP1 in lung cancer is still not clear. Analysis at allelic levels cannot fully explain the function of PARP1 on lung cancer. Our study aims to further explore the relation between PARP1 haplotypes and lung cancer. MATERIALS AND METHODS DNA and RNA were extracted from non-small cell lung cancer (NSCLC) tumor and adjacent normal fresh frozen tissue. Five PARP1-SNPs were genotyped and PARP1-specific SNPs were imputed using IMPUTE and SHAPEIT software. The SNPs were subjected to allelic, haplotype and SNP-SNP interaction analyses. Correlation between SNPs and mRNA/protein expressions were performed. RESULTS SNP imputation inferred the ungenotyped SNPs and increased the power for association analysis. Tumor tissue samples are more likely to carry rs1805414 (OR = 1.85; 95% CI: 1.12-3.06; P-value: 0.017) and rs1805404 (OR = 2.74; 95%CI 1.19-6.32; P-value: 0.015) compared to normal tissues. Our study is the first study to show that haplotypes comprising of 5 SNPs on PARP1 (rs1136410, rs3219073, rs1805414, rs1805404, rs1805415) is able to differentiate the NSCLC tumor from normal tissues. Interaction between rs3219073, rs1805415, and rs1805414 were significantly associated with the NSCLC tumor with OR ranging from 3.61-6.75; 95%CI from 1.82 to 19.9; P-value<0.001. CONCLUSION PARP1 haplotypes may serve as a better predictor in lung cancer development and prognosis compared to single alleles.
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Affiliation(s)
- Jing Jin
- Department of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America
| | - Heather Robeson
- Department of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America
| | - Pebbles Fagan
- Department of Health Behavior and Health Education, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America
- Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America
- Center for the Studies of Tobacco, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America
| | - Mohammed S. Orloff
- Department of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America
- Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America
- Center for the Studies of Tobacco, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America
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Effects of Shinrin-Yoku (Forest Bathing) and Nature Therapy on Mental Health: a Systematic Review and Meta-analysis. Int J Ment Health Addict 2020. [DOI: 10.1007/s11469-020-00363-4] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
AbstractShinrin-yoku, immersing oneself in nature using one’s senses, has been receiving increased attention internationally. While most of the existing studies have focused on physical health, this systematic review and meta-analysis examined the mental health impacts of shinrin-yoku, using the PRISMA guidelines (PROSPERO registry: BLINDED). Of 497 articles retrieved on databases including PubMed/MEDLINE, PsycINFO, Science Direct and Google Scholar, twenty met the inclusion criteria. All studies were conducted in Asia and Europe, and used a variety of different bathing approaches (e.g. breathing, walking, yoga). While noting a need for more rigorous research and extensive follow-up assessments, the findings indicate that shinrin-yoku can be effective in reducing mental health symptoms in the short term, particularly anxiety. More careful examination of shinrin-yoku practices is needed; longer follow-up with participants from a range of countries along with greater examination of potential mechanisms is needed for shinrin-yoku to be accepted into mainstream interventions.
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Xing PY, Wang SZ, Shi JF, Wang L, Hui ZG, Ren JS, Liu SM, Qiao YL, Dai M, Li JL. Changes and Influential Factors of Chemotherapy Usage for Non-Small Cell Lung Cancer Patients in China: A Multicenter 10-Year (2005-2014) Retrospective Study. Cancer Manag Res 2020; 12:6033-6044. [PMID: 32765102 PMCID: PMC7381789 DOI: 10.2147/cmar.s253789] [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: 03/13/2020] [Accepted: 06/09/2020] [Indexed: 11/25/2022] Open
Abstract
Background Chemotherapy has improved the survival of non-small cell lung cancer (NSCLC) patients over the past few decades. However, there have not been any epidemiological studies on chemotherapy for Chinese NSCLC patients. Patients and Methods The patients diagnosed as primary lung cancer between January 1, 2005, and December 31, 2014, in eight hospitals from eight provinces in China were retrospectively reviewed. Demographic and clinical data were extracted from medical history systems. Chi-square test and logistic regression were used to analyze the changes of chemotherapy usage and influential factors. Results A total of 7184 lung cancer cases were eligible, among which 6481 NSCLC cases were included in this analysis. Among stage I/II patients, the percentages of receiving adjuvant chemotherapy did not change significantly between the earlier (28.5%) and the latter five years (25.7%) (p = 0.1288). Among stage IIIA patients, the percentages of chemotherapy usage did not change significantly between the earlier and the latter five years in neo-adjuvant (7.5% vs 5.6%, p = 0.1478) and adjuvant (23.1% vs 26.8%, p = 0.1129) treatment. The proportions of first-line platinum-based doublets for stage IIIB/IV patients changed significantly over the 10 years (p < 0.0001). Patients from provinces with inferior gross domestic product, with lower medical reimbursement rates and without smoking history were more likely to use the docetaxel/paclitaxel doublets, comparing with the gemcitabine doublets. Conclusion From 2005 to 2014, there was no significant change in the chemotherapy pattern of early NSCLC. Economic factors mainly contributed to the significant changes in the first-line chemotherapy regimen selection for advanced patients.
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Affiliation(s)
- Pu-Yuan Xing
- Department of Medical 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
| | - Shou-Zheng Wang
- Department of Medical 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
| | - Ju-Fang Shi
- Office of Cancer Screening, 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
| | - Le Wang
- Office of Cancer Screening, 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
| | - Zhou-Guang Hui
- Department of Radiation 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
| | - Jian-Song Ren
- Office of Cancer Screening, 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
| | - Shang-Mei Liu
- Department of Pathology, 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
| | - You-Lin Qiao
- Department of Epidemiology, 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
| | - Min Dai
- Office of Cancer Screening, 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
| | - Jun-Ling Li
- Department of Medical 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
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Young Z, Moghaddam N, Tickle A. The Efficacy of Cognitive Behavioral Therapy for Adults With ADHD: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Atten Disord 2020; 24:875-888. [PMID: 27554190 DOI: 10.1177/1087054716664413] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Objective: To systematically review the literature on published randomized controlled trials (RCTs) of cognitive behavioral therapy (CBT) for adult ADHD and to establish the effectiveness of CBT in reducing ADHD symptoms. Method: A systematic review of nine RCTs and two subsequent meta-analyses of eight of the studies were conducted. Results: Just nine studies were identified, of generally good quality but with some limitations. Four trials (total N = 160) compared CBT with waiting list controls, and three trials (total N = 191) compared CBT with appropriate active control groups. Meta-analyses showed that CBT was superior to waiting list with a moderate to large effect size (standardized mean difference [SMD] = 0.76, 95% confidence interval [CI] [0.21, 1.31], p = .006) and superior to active control groups with a small to moderate effect size (SMD = 0.43, 95% CI [0.14, 0.71], p = .004). Conclusion: These results give support to the efficacy of CBT in reducing symptoms of ADHD post-intervention.
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Affiliation(s)
| | | | - Anna Tickle
- The University of Nottingham, UK.,Nottinghamshire Healthcare NHS Foundation Trust, Nottingham, UK
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Gao J, Song L, Xia H, Peng L, Wen Z. 6'-O-galloylpaeoniflorin regulates proliferation and metastasis of non-small cell lung cancer through AMPK/miR-299-5p/ATF2 axis. Respir Res 2020; 21:39. [PMID: 32014006 PMCID: PMC6998290 DOI: 10.1186/s12931-020-1277-6] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 01/03/2020] [Indexed: 12/20/2022] Open
Abstract
Background Recent studies have shown 6'-O-galloylpaeoniflorin (GPF), a nature product extracted from the roots of paeoniflorin exerts anti-oxidant and anti-inflammatory activities. However, the effects of GPF on the proliferation and invasion in non-small cell lung cancer (NSCLC) cells have not been clarified. Methods MTT assay was performed to determine the cytotoxicity of GPF treatment on NSCLC cells. Colony formation assay, cell scratch test and transwell assay were performed to determine the proliferation and invasion of NSCLC cells in vitro, respectively. An A549 cell xenograft mouse model was performed to confirm the growth of NSCLC cells in vivo. Western blotting was used to measure the levels of activating transcription factor 2 (ATF2), AMP-activated protein kinase (AMPK) and phosph-AMPK (p-AMPK). Luciferase assay was used to validate the binding of miR-299-5p on the 3' untranslated region (UTR) of ATF2. Results Administration of GPF (50 or 100 μM) was significantly cytotoxic to A549 cells and H1299 cells, as well as inhibited the clonality, invasion and metastasis of NSCLC cells in vitro. GPF treatment also inhibited the tumor growth of NSCLC cell mouse xenografts in vivo. Exotic expression of miR-299-5p significantly inhibited the growth of NSCLC cells in vitro and in vivo. Downregulation of miR-299-5p expression attenuated the inhibition of the proliferation and metastasis of non-small cell lung cancer cells by GPF treatment. miR-299-5p significantly decreased ATF2 mRNA and protein levels in A549 cells (p < 0.05). Overexpression of ATF2 blocked the inhibitory effect of miR-299-5p on the proliferation and invasiveness of A549 cells. Conclusions GPF regulates miR-299-5p/ATF2 axis in A549 cells via the AMPK signalling pathway, thereby inhibiting the proliferation and metastasis of non-small cell lung cancer cells.
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Affiliation(s)
- Jinying Gao
- Department of Respiratory Medicine, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Lei Song
- Department of Respiratory Medicine, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Huan Xia
- Department of Respiratory Medicine, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, First Hospital of Jilin University, Changchun, Jilin Province, China
| | - Liping Peng
- Department of Respiratory Medicine, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, First Hospital of Jilin University, Changchun, Jilin Province, China.
| | - Zhongmei Wen
- Department of Respiratory Medicine, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, First Hospital of Jilin University, Changchun, Jilin Province, China.
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9
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Liu J, Yao Y, Hu Z, Zhou H, Zhong M. Transcriptional profiling of long-intergenic noncoding RNAs in lung squamous cell carcinoma and its value in diagnosis and prognosis. Mol Genet Genomic Med 2019; 7:e994. [PMID: 31617686 PMCID: PMC6900396 DOI: 10.1002/mgg3.994] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 07/10/2019] [Accepted: 09/03/2019] [Indexed: 12/14/2022] Open
Abstract
Background Long intergenic noncoding RNAs (lincRNAs) are a series of novel transcribed regions expressed in cancers that may represent candidate biomarkers for lung squamous cell carcinoma (LSqCC) treatment. In this study, we evaluated the lincRNA profile in LSqCC patients and screened valuable lincRNAs for diagnosis and prognosis. Methods Transcriptome profiling of 549 samples derived from 501 LSqCC patients were identified in TCGA database. 48 patients had paired primary tumor (PT) and solid normal (SN) tissue samples, while 453 patients had only PT samples. 1,771 lincRNA candidates were evaluated. Paired test (Wilcoxon two‐sample paired signed rank tests) was performed in paired PT and SN samples. Logistic regression analysis were performed in independent 453 PT samples and 48 SN samples to screen the significant lincRNAs candidates for malignances. Independent 501 PT samples were further used to screen the significant lincRNAs candidates for prognosis. Results Among 1,771 lincRNAs, 10 lincRNAs were significant highly‐expressed risk candidates in PT samples, and 10 protective lincRNAs candidates were significant lowly‐expressed in PT samples. Among 10 highly‐expressed risk lincRNAs, a small panel of LINC00487, LINC01927, and C10orf143 (LINC00959) could effectively predict malignancies in paired samples (AUC = 0.7274, 95%CI = (0.6264, 0.8285)). When combined with protective lincRNA candidates LINC02315, LINC00491, and LINC01697, the predictive efficiency was greatly improved in both paired samples (AUC = 0.8030, 95%CI = (0.7250, 0.8810)) and independent samples (AUC = 0.7481, 95%CI= (0.6642, 0.8320)). Additionally, three highly‐expressed risk lincRNAs, LINC01031, LINC01088, and LINC01931, were significantly associated with poor prognosis in PT samples, suggesting potential targets for anti‐LSqCC treatment. Conclusion Therefore, lincRNAs could be promising biomarkers for predicting malignancies and potential anti‐LSqCC targets for drug development.
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Affiliation(s)
- Jieqiong Liu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.,The First Hospital of Changsha City, Changsha, China
| | - Yali Yao
- The First Hospital of Changsha City, Changsha, China
| | - Zheyu Hu
- Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Hui Zhou
- Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Meizuo Zhong
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
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10
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Gallacher D, Armoiry X, Auguste P, Court R, Mantopoulos T, Patterson J, De Santis M, Cresswell J, Mistry H. Pembrolizumab for Previously Treated Advanced or Metastatic Urothelial Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. PHARMACOECONOMICS 2019; 37:19-27. [PMID: 30030817 DOI: 10.1007/s40273-018-0689-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Pembrolizumab is an intravenously administered monoclonal antibody licensed for locally advanced or metastatic urothelial carcinoma after platinum-containing chemotherapy. This summary presents the perspective of Warwick Evidence, the Evidence Review Group (ERG) appointed by the National Institute of Health and Care Excellence (NICE) for the single technology appraisal of pembrolizumab for this indication. Pembrolizumab is manufactured by Merck, Sharp and Dohme (MSD). The major source of clinical effectiveness was the KEYNOTE-045 trial, where 542 patients received either pembrolizumab or clinician's choice of docetaxel, paclitaxel or vinflunine as a second-line treatment. No indirect treatment comparison was performed. The clinical effectiveness was assessed using hazard ratios for overall survival (OS) and progression-free survival (PFS) of the intention-to-treat (ITT) population, together with the subpopulations positive for programmed cell death 1 ligand 1 (PD-L1) expression (combined positive score [CPS] ≥ 1%) and strongly positive for PD-L1 expression (CPS ≥ 10%). In the ITT population, OS improved with pembrolizumab (HR 0.73, 95% CI 0.59-0.91) while PFS outcomes showed no difference (HR 0.98, 95% CI 0.81-1.19). Pembrolizumab demonstrated a better safety profile than its combined comparators, with fewer patients experiencing adverse events (60.9 vs 90.2%). Similar results were observed in populations expressing PD-L1. MSD estimated the cost effectiveness of pembrolizumab using a de novo partitioned survival model. The model had three health states: pre-progression, post-progression and death, where OS and PFS estimates excluded patients who received vinflunine. The largest uncertainty was over the selection of the parametric models used to extrapolate OS and PFS and the time point for when to begin their extrapolation. The company preferences for extrapolation were not well supported and the ERG disagreed with their selection for OS. Utility values were also contentious, with the company preferring to use pooled time-to-death-based utilities pooled across treatment arms, whilst the ERG preferred pooled progression-based utilities. The company preferred to use data from patients receiving vinflunine when calculating the utility values, which the ERG disagreed with as this is not recommended treatment within the UK. The company assumed a lifetime treatment effect for their model; however, the lack of evidence made it difficult to confidently provide a realistic estimate of treatment effect duration. Various durations were explored (3, 5 and 10 years). The first appraisal committee meeting concluded that pembrolizumab was not cost effective, largely due to uncertainty in the OS and PFS extrapolations. The company's second submission included an additional 4 months follow-up to survival data. The company in this new submission maintained their original assumptions in their base-case analysis, changing only the choice of parametric curve for PFS. This change resulted in the OS and PFS curves intersecting at 6 years in the pembrolizumab arm, at which point PFS identically followed OS. This resulted in no patients in the post-progression health state beyond this time point, and therefore, the majority of pembrolizumab's benefit came from pre-progression survival. Given the unclear PFS benefit, the ERG found this implausible and maintained their original base-case model assumptions. Considerable uncertainty remained over the specification of the extrapolations and the duration of treatment effect. Based on a new-value proposition submitted by the company, the appraisal committee concluded that pembrolizumab had plausible potential to be cost effective. Pembrolizumab was referred for funding through the Cancer Drugs Fund, so that further data could be collected with the aim of diminishing the outstanding uncertainties pertaining to its clinical effectiveness.
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Affiliation(s)
- Daniel Gallacher
- Warwick Evidence, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK
| | - Xavier Armoiry
- Warwick Evidence, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK
| | - Peter Auguste
- Warwick Evidence, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK
| | - Rachel Court
- Warwick Evidence, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK
| | - Theodoros Mantopoulos
- Warwick Evidence, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK
| | | | - Maria De Santis
- Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK
- Charité Universitätsmedizin, Berlin, Germany
| | - Joanne Cresswell
- Urology Department, The James Cook University Hospital, Marton Road, Middlesbrough, TS4 3BW, UK
| | - Hema Mistry
- Warwick Evidence, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK.
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11
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Hu X, Hay JW. First-line pembrolizumab in PD-L1 positive non-small-cell lung cancer: A cost-effectiveness analysis from the UK health care perspective. Lung Cancer 2018; 123:166-171. [PMID: 30089590 DOI: 10.1016/j.lungcan.2018.07.012] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 07/10/2018] [Accepted: 07/11/2018] [Indexed: 10/28/2022]
Abstract
BACKGROUND Pembrolizumab has shown significant survival benefits in treating chemotherapy-naïve non-small-cell lung cancer patients (NSCLC) with increased level of PD-L1 expression. This analysis aimed to evaluate the cost-effectiveness of pembrolizumab as a first-line treatment for patients with PD-L1 positive NSCLC from the UK health care perspective. METHODS A Markov model with progression-free, progressive disease and death states was developed. Clinical parameters were informed by the KEYNOTE-024 trial. Utility values were sourced from published literature. Cost data including drug acquisition costs, disease management costs, and adverse event costs were derived from British National Formulary and published literature. The model was run until 99% patients died. Both health outcomes and costs were discounted at an annual rate of 3.5%. Deterministic and probabilistic sensitivity analyses were performed to address the uncertainties around model parameters. RESULTS In the base case, pembrolizumab is projected to increase patient's life expectancy by 1.32 life-years over chemotherapy (2.45 vs. 1.13) and 0.83 QALYs (1.55 vs. 0.71) at an additional cost of £72,465, yielding an incremental cost-effectiveness ratio of £86,913/QALY. When parameters were varied in the deterministic sensitivity analyses, results are most sensitive to duration of median overall survival in both groups. Probability sensitivity analyses showed that using a willingness-to-pay threshold of £50,000 per QALY, the probability of pembrolizumab being cost-effective is 29.4%. CONCLUSION Using a willingness-to-pay threshold of £50,000, pembrolizumab is not cost-effective at its current list price and a discount of 50% or more is required for it to be cost-effective comparing to commonly prescribed chemotherapy. Risk-sharing contracts may be helpful in resolving some of the underlying uncertainty associated with the long-term survival and varying extent of patient response.
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Affiliation(s)
- Xiaohan Hu
- USC Leonard D. Schaeffer Center for Health Policy and Economics, 635 Downey Way, Verna & Peter Dauterive Hall (VPD) Suite 210, Los Angeles, CA, 90089, United States.
| | - Joel W Hay
- USC Leonard D. Schaeffer Center for Health Policy and Economics, 635 Downey Way, Verna & Peter Dauterive Hall (VPD) Suite 210, Los Angeles, CA, 90089, United States.
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12
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Zhang YH, Lu Y, Lu H, Zhang MW, Zhou YM, Li XL, Lv P, Zhao XY. Pre-treatment hemoglobin levels are an independent prognostic factor in patients with non-small cell lung cancer. Mol Clin Oncol 2018; 9:44-49. [PMID: 29896399 DOI: 10.3892/mco.2018.1628] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 05/09/2018] [Indexed: 12/19/2022] Open
Abstract
To date, few studies have reported the prognostic value of pre-treatment hemoglobin levels in patients with non-small cell lung cancer (NSCLC). In the present study, 416 patients with NSCLC were retrospectively reviewed. Univariate Cox proportional hazards regression analysis demonstrated that patients with normal pre-treatment hemoglobin (NPHb) levels had a greater chance of surviving for longer period, than did patients with low pre-treatment hemoglobin (LPHb) levels (HR, 2.05; 95% CI, 1.63-2.57; P<0.001). After adjustment for age, sex, tumor-node-metastasis stage, Karnofsky performance status, lung lobectomy, chemotherapy and radiotherapy, multivariate Cox proportional hazards regression analysis revealed that LPHb was an independent predictor for the poor prognosis of patients with NSCLC (HR, 1.86; 95% CI, 1.47-2.36; P<0.001). Estimation of the cumulative survival revealed that the overall survival of NPHb patients was significantly higher than that for LBHb patients (P<0.05), independent of whether the patients had received lung lobectomy or chemotherapy treatments. In conclusion, low pre-treatment hemoglobin levels were demonstrated to be an independent biomarker for poor prognosis in patients with NSCLC.
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Affiliation(s)
- Yue-Hua Zhang
- Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, Henan 475001, P.R. China.,Department of Oncology, The First Affiliated Hospital of Henan University, Kaifeng, Henan 475001, P.R. China
| | - Yuquan Lu
- International Joint Research Laboratory for Cell Medical Engineering of Henan, Huaihe Hospital of Henan University, Kaifeng, Henan 475001, P.R. China
| | - Hong Lu
- Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, Henan 475001, P.R. China
| | - Meng-Wei Zhang
- Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, Henan 475001, P.R. China
| | - Yue-Min Zhou
- International Joint Research Laboratory for Cell Medical Engineering of Henan, Huaihe Hospital of Henan University, Kaifeng, Henan 475001, P.R. China.,Center for Translational Medicine, Huaihe Hospital of Henan University, Kaifeng, Henan 475001, P.R. China
| | - Xiang-Lei Li
- Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, Henan 475001, P.R. China
| | - Pin Lv
- Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, Henan 475001, P.R. China
| | - Xiao-Yan Zhao
- Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, Henan 475001, P.R. China
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13
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Wei X, Li Q, Li Y, Duan W, Huang C, Zheng X, Sun L, Luo J, Wang D, Zhang S, Xin X, Gao M. Prediction of survival prognosis of non-small cell lung cancer by APE1 through regulation of Epithelial-Mesenchymal Transition. Oncotarget 2017; 7:28523-39. [PMID: 27074577 PMCID: PMC5053743 DOI: 10.18632/oncotarget.8660] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Accepted: 03/28/2016] [Indexed: 12/23/2022] Open
Abstract
The DNA base excision repair gene APE1 involves in DNA damage repair pathway and overexpression in a variety of human cancers. Analyses of patients with non-small cell lung cancer (NSCLC) suggested that multiple factors associated with prognosis of NSCLC patients. Further investigation showed that APE1 expression was able to predict the progression-free survival and overall survival in patients with NSCLC and correlated with lymph node metastasis. Intriguingly, as a stratification of APE1-141 SNPs in APE1 positive expression, we also found APE1-141 GT/GG was identified as a marker for prediction of poor survival in NSCLC patients. In the in vitro experiments, the results showed that when APE1 expression was inhibited by siRNA or AT101 (an APE1 inhibitor), the migration and invasion of NSCLC cells were suppressed. Furthermore, epithelial-mesenchymal transition (EMT) markers was tested to provide evidence that APE1 promoted NSCLC EMT through interaction with SirT1. Using NSCLC xenograft models, we confirmed that AT101 shrank tumor volumes and inhibited lymph node metastasis. In conclusion, APE1 could be a potential target for patients with NSCLC metastasis and AT101 is a potent inhibitor in further treatment of NSCLC patients.
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Affiliation(s)
- Xi Wei
- Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Qing Li
- Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China
| | - Ying Li
- The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Wei Duan
- Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China
| | - Chongbiao Huang
- Department of Senior Ward, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Xiangqian Zheng
- Department of Thyroid and Cervical Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Lei Sun
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Jingtao Luo
- The Department of Otorhinolaryngology and Maxillofacial Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, National Clinical Research Center of Cancer, Tianjin, China
| | - Dong Wang
- Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China
| | - Sheng Zhang
- Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Xiaojie Xin
- Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Ming Gao
- Department of Thyroid and Cervical Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
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14
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Albaba H, Lim C, Leighl NB. Economic Considerations in the Use of Novel Targeted Therapies for Lung Cancer: Review of Current Literature. PHARMACOECONOMICS 2017; 35:1195-1209. [PMID: 28861770 DOI: 10.1007/s40273-017-0563-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Lung cancer remains the leading cause of cancer-related death and economic burden worldwide. Despite the heavy toll of lung cancer, multiple new advances have improved patient outcomes, largely through precision medicine and targeted therapy. The associated rising economic burden however may impact the uptake of novel therapeutic agents in lung cancer, thereby limiting patient access. This article identifies and reviews economic evaluations of targeted agents in lung cancer in the era of precision medicine. Articles evaluating biomarker-directed test-and-treat strategies are also reviewed to evaluate the cost impact of novel therapeutic agents at a population level. The Quality of Health Economic Studies instrument is applied to assess the quality of included studies. Forty-six studies are reviewed and encompass studies of epidermal growth factor receptor inhibitors and monoclonal antibodies, anaplastic lymphoma kinase inhibitors, vascular endothelial growth factor and vascular endothelial growth factor receptor inhibitors and immunotherapy (programmed death-1 inhibitors). Key factors influencing results of economic analyses include comparators chosen, perspective used, magnitude of clinical benefit, utility weighting of outcomes and drug acquisition costs. Biomarker-driven decision making should be integrated into cost evaluations given the important role of molecular testing for individualising treatment for non-small-cell lung cancer. We conclude that despite major clinical advances in lung cancer therapeutics, cost remains an important consideration in the adoption of novel therapies.
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Affiliation(s)
- Hamzeh Albaba
- Princess Margaret Cancer Center, University Health Network, c/o 700 University Avenue, Room 7-913, Toronto, ON, M5G 1Z5, Canada
- University of Toronto, Toronto, ON, Canada
| | - Charles Lim
- Princess Margaret Cancer Center, University Health Network, c/o 700 University Avenue, Room 7-913, Toronto, ON, M5G 1Z5, Canada
- University of Toronto, Toronto, ON, Canada
| | - Natasha B Leighl
- Princess Margaret Cancer Center, University Health Network, c/o 700 University Avenue, Room 7-913, Toronto, ON, M5G 1Z5, Canada.
- University of Toronto, Toronto, ON, Canada.
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15
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Kuo WT, Tu DG, Chiu LY, Sheu GT, Wu MF. High pemetrexed sensitivity of docetaxel-resistant A549 cells is mediated by TP53 status and downregulated thymidylate synthase. Oncol Rep 2017; 38:2787-2795. [PMID: 28901493 PMCID: PMC5780031 DOI: 10.3892/or.2017.5951] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 08/02/2017] [Indexed: 01/08/2023] Open
Abstract
The chemoresistance of non-small cell lung cancer (NSCLC) that occurs in docetaxel (DOC) chemotherapy substantially decreases the survival of patients. To overcome DOC-induced chemoresistance, we established DOC-selected A549 lung cancer sublines (A549/D16 and A549/D32) and revealed that both sublines were cross-resistant to vincristine (VCR) and doxorubicin (DXR). Notably, both sublines were more sensitive to pemetrexed (PEM) than parental cells according to MTT and clonogenic assays. The expression levels of thymidylate synthase (TS) and γ-glutamyl hydrolase (GGH) were downregulated in DOC-resistant sublines. When exogenous TS was overexpressed in A549/D16 cells, PEM sensitivity was significantly decreased, however it was not decreased by overexpression of exogenous GGH. PEM treatment induced more apoptotic sub-G1 cells in both DOC-resistant sublines and in the in vivo PEM sensitivities of A549/D16 cells. These findings were further confirmed by a xenografted tumor model. To unmask the mediator of TS downregulation, we investigated human lung cancer cell lines that have various TP53 statuses using DOC treatment. The level of TS protein was significantly decreased in wild-type TP53-containing cells with DOC treatment; TS expression levels were not affected in mutant-TP53 and TP53-null cells under the same conditions. Furthermore, when the expression of TP53 was inhibited in A549 cells, the expression level of TS was increased. Our data indicated that DOC activated wild-type TP53 and suppressed TS expression under continuous DOC exposure. Therefore, the expression of TS remained at low levels in DOC-resistant A549 cancer cells. Our data revealed that for lung cancer with DOC resistance and wild-type TP53 status, the administration of PEM as a second-line agent to overcome DOC-resistance may benefit patients.
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Affiliation(s)
- Wei-Ting Kuo
- Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan, R.O.C
| | - Dom-Gene Tu
- Department of Nuclear Medicine, Ditmanson Medical Foundation, Chia‑Yi Christian Hospital, Chiayi City 60002, Taiwan, R.O.C
| | - Ling-Yen Chiu
- Institute of Medicine, Chung Shan Medical University Hospital, Taichung City 402, Taiwan, R.O.C
| | - Gwo-Tarng Sheu
- Institute of Medicine, Chung Shan Medical University Hospital, Taichung City 402, Taiwan, R.O.C
| | - Ming-Fang Wu
- School of Medicine, Chung Shan Medical University Hospital, Taichung City 402, Taiwan, R.O.C
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16
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Taipale K, Winfree KB, Boye M, Basson M, Sleilaty G, Eaton J, Evans R, Chouaid C. A cost-effectiveness analysis of first-line induction and maintenance treatment sequences in patients with advanced nonsquamous non-small-cell lung cancer in France. CLINICOECONOMICS AND OUTCOMES RESEARCH 2017; 9:505-518. [PMID: 28860832 PMCID: PMC5566359 DOI: 10.2147/ceor.s128371] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background Comparative effectiveness and cost-effectiveness data for induction–maintenance (I–M) sequences for the treatment of patients with nonsquamous non-small-cell lung cancer (nsqNSCLC) are limited because of a lack of direct evidence. This analysis aimed to compare the cost-effectiveness of I–M pemetrexed with those of other I–M regimens used for the treatment of patients with advanced nsqNSCLC in the French health-care setting. Materials and methods A previously developed global partitioned survival model was adapted to the France-only setting by restricting treatment sequences to include 12 I–M regimens most relevant to France, and incorporating French costs and resource-use data. Following a systematic literature review, network meta-analyses were performed to obtain hazard ratios for progression-free survival (PFS) and overall survival (OS) relative to gemcitabine + cisplatin (induction sequences) or best supportive care (BSC) (maintenance sequences). Modeled health-care benefits were expressed as life-years (LYs) and quality-adjusted LYs (QALYs) (estimated using French EuroQol five-dimension questionnaire tariffs). The study was conducted from the payer perspective (National Health Insurance). Cost- and benefit-model inputs were discounted at an annual rate of 4%. Results Base-case results showed pemetrexed + cisplatin induction followed by (→) pemetrexed maintenance had the longest mean OS and PFS and highest LYs and QALYs. Costs ranged from €12,762 for paclitaxel + carboplatin → BSC to €35,617 for pemetrexed + cisplatin → pemetrexed (2015 values). Gemcitabine + cisplatin → BSC, pemetrexed + cisplatin → BSC, and pemetrexed + cisplatin → pemetrexed were associated with fully incremental cost-effectiveness ratios (ICERs) of €16,593, €80,656, and €102,179, respectively, per QALY gained versus paclitaxel + carboplatin → BSC. All other treatment sequences were either dominated (ie, another sequence had lower costs and better/equivalent outcomes) or extendedly dominated (ie, the comparator had a higher ICER than a more effective comparator) in the model. Sensitivity analyses showed the model to be relatively insensitive to plausible changes in the main assumptions, with none increasing or decreasing the ICER by more than ~€20,000 per QALY gained. Conclusion In the absence of direct comparative trial evidence, this cost-effectiveness analysis indicated that of a large number of I–M sequences used for the treatment of patients with nsqNSCLC in France, pemetrexed + cisplatin → pemetrexed achieved the best clinical outcomes (0.28 incremental QALYs gained) versus paclitaxel + carboplatin → BSC.
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Affiliation(s)
- Kaisa Taipale
- Global Patient Outcomes and Real World Evidence International, Oy Eli Lilly Finland AB, Helsinki, Finland
| | - Katherine B Winfree
- Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA
| | - Mark Boye
- Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA
| | - Mickael Basson
- Corporate Affairs, Lilly France, Neuilly-sur-Seine, France
| | - Ghassan Sleilaty
- Bio-Medicines Medical Affairs, Lilly France, Neuilly-sur-Seine, France
| | - James Eaton
- ICON Health Economics and Epidemiology, ICON Plc, Milton Park, UK
| | - Rachel Evans
- ICON Health Economics and Epidemiology, ICON Plc, Milton Park, UK
| | - Christos Chouaid
- Thoracic Oncology, Service de Pneumologie, Centre Hospitalier Intercommunal Créteil, Créteil, France
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17
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Azar FE, Azami-Aghdash S, Pournaghi-Azar F, Mazdaki A, Rezapour A, Ebrahimi P, Yousefzadeh N. Cost-effectiveness of lung cancer screening and treatment methods: a systematic review of systematic reviews. BMC Health Serv Res 2017; 17:413. [PMID: 28629461 PMCID: PMC5477275 DOI: 10.1186/s12913-017-2374-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Accepted: 06/09/2017] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Due to extensive literature in the field of lung cancer and their heterogeneous results, the aim of this study was to systematically review of systematic reviews studies which reviewed the cost-effectiveness of various lung cancer screening and treatment methods. METHODS In this systematic review of systematic reviews study, required data were collected searching the following key words which selected from Mesh: "lung cancer", "lung oncology", "lung Carcinoma", "lung neoplasm", "lung tumors", "cost- effectiveness", "systematic review" and "Meta-analysis". The following databases were searched: PubMed, Cochrane Library electronic databases, Google Scholar, and Scopus. Two reviewers (RA and A-AS) evaluated the articles according to the checklist of "assessment of multiple systematic reviews" (AMSTAR) tool. RESULTS Overall, information of 110 papers was discussed in eight systematic reviews. Authors focused on cost-effectiveness of lung cancer treatments in five systematic reviews. Targeted therapy options (bevacizumab, Erlotinib and Crizotinib) show an acceptable cost-effectiveness. Results of three studies failed to show cost-effectiveness of screening methods. None of the studies had used the meta-analysis method. The Quality of Health Economic Studies (QHES) tool and Drummond checklist were mostly used in assessing the quality of articles. Most perspective was related to the Payer (64 times) and the lowest was related to Social (11times). Most cases referred to Incremental analysis (82%) and also the lowest point of referral was related to Discounting (in 49% of the cases). The average quality score of included studies was calculated 9.2% from 11. CONCLUSIONS Targeted therapy can be an option for the treatment of lung cancer. Evaluation of the cost-effectiveness of computerized tomographic colonography (CTC) in lung cancer screening is recommended. The perspective of the community should be more taken into consideration in studies of cost-effectiveness. Paying more attention to the topic of Discounting will be necessary in the studies.
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Affiliation(s)
| | - Saber Azami-Aghdash
- Road Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Pournaghi-Azar
- Dental and Periodental Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Mazdaki
- Health Management and Economics Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Aziz Rezapour
- Health Management and Economics Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Parvin Ebrahimi
- Department of Health service Management, School of Health Management and Information Sciences & Health Management and Economics Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Negar Yousefzadeh
- Health Management and Economics Research Center, Iran University of Medical Sciences, Tehran, Iran
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18
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Greenhalgh J, Bagust A, Boland A, Dwan K, Beale S, Hockenhull J, Proudlove C, Dundar Y, Richardson M, Dickson R, Mullard A, Marshall E. Erlotinib and gefitinib for treating non-small cell lung cancer that has progressed following prior chemotherapy (review of NICE technology appraisals 162 and 175): a systematic review and economic evaluation. Health Technol Assess 2016; 19:1-134. [PMID: 26134145 DOI: 10.3310/hta19470] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Lung cancer is the second most diagnosed cancer in the UK. Over 70% of lung cancers are non-small cell lung cancers (NSCLCs). Patients with stage III or IV NSCLC may be offered treatment to improve survival, disease control and quality of life. One-third of these patients receive further treatment following disease progression; these treatments are the focus of this systematic review. OBJECTIVES To appraise the clinical effectiveness and cost-effectiveness of erlotinib [Tarceva(®), Roche (UK) Ltd] and gefitinib (IRESSA(®), AstraZeneca) compared with each other, docetaxel or best supportive care (BSC) for the treatment of NSCLC after disease progression following prior chemotherapy. The effectiveness of treatment with gefitinib was considered only for patients with epidermal growth factor mutation-positive (EGFR M+) disease. DATA SOURCES Four electronic databases (EMBASE, MEDLINE, The Cochrane Library, PubMed) were searched for randomised controlled trials (RCTs) and economic evaluations. Manufacturers' evidence submissions to the National Institute for Health and Care Excellence were also considered. REVIEW METHODS Outcomes for three distinct patient groups based on EGFR mutation status [EGFR M+, epidermal growth factor mutation negative (EGFR M-) and epidermal growth factor mutation status unknown (EGFR unknown)] were considered. Heterogeneity of the data precluded statistical analysis. A de novo economic model was developed to compare treatments (incremental cost per quality-adjusted life-year gained). RESULTS Twelve trials were included in the review. The use of gefitinib was compared with chemotherapy (n = 6) or BSC (n = 1), and the use of erlotinib was compared with chemotherapy (n = 3) or BSC (n = 1). One trial compared the use of gefitinib with the use of erlotinib. No trials included solely EGFR M+ patients; all data were derived from retrospective subgroup analyses from six RCTs [Kim ST, Uhm JE, Lee J, Sun JM, Sohn I, Kim SW, et al. Randomized phase II study of gefitinib versus erlotinib in patients with advanced non-small cell lung cancer who failed previous chemotherapy. Lung Cancer 2012;75:82-8, V-15-32, Tarceva In Treatment of Advanced NSCLC (TITAN), BR.21, IRESSA Survival Evaluation in Lung cancer (ISEL) and IRESSA NSCLC Trial Evaluating REsponse and Survival versus Taxotere (INTEREST)]. These limited data precluded conclusions regarding the clinical effectiveness of any treatment for EGFR M+ patients. For EGFR M- patients, data were derived from the TArceva Italian Lung Optimization tRial (TAILOR) trial and Docetaxel and Erlotinib Lung Cancer Trial (DELTA). Retrospective data were also derived from subgroup analyses of BR.21, Kim et al., TITAN, INTEREST and ISEL. The only statistically significant reported results were for progression-free survival (PFS) for TAILOR and DELTA, and favoured docetaxel over erlotinib [TAILOR hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.06 to 1.82; DELTA HR 1.44, 95% CI 1.08 to 1.92]. In EGFR unknown patients, nine trials (INTEREST, IRESSA as Second-line Therapy in Advanced NSCLC - KoreA, Li, Second-line Indication of Gefitinib in NSCLC, V-15-32, ISEL, DELTA, TITAN and BR.21) reported overall survival data and only one (BR.21) reported a statistically significant result favouring the use of erlotinib over BSC (HR 0.7, 95% CI 0.58 to 0.85). For PFS, BR.21 favoured the use of erlotinib when compared with BSC (HR 0.61, 95% CI 0.51 to 0.74) and the use of gefitinib was favoured when compared with BSC (HR 0.82, 95% CI 0.73 to 0.92) in ISEL. Limitations in the clinical data precluded assessment of cost-effectiveness of treatments for an EGFR M+ population by the Assessment Group (AG). The AG's economic model suggested that for the EGFR M- population, the use of erlotinib was not cost-effective compared with the use of docetaxel and compared with BSC. For EGFR unknown patients, the use of erlotinib was not cost-effective when compared with BSC. CONCLUSIONS/FUTURE WORK The lack of clinical data available for distinct patient populations limited the conclusions of the assessment. Future trials should distinguish between patients with EGFR M+ and EGFR M- disease. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Janette Greenhalgh
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Adrian Bagust
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Angela Boland
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Kerry Dwan
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Sophie Beale
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Juliet Hockenhull
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Christine Proudlove
- North West Medicines Information Centre, Pharmacy Practice Unit, Liverpool, UK
| | - Yenal Dundar
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Marty Richardson
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Rumona Dickson
- Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK
| | - Anna Mullard
- The Clatterbridge Centre NHS Foundation Trust, Liverpool, UK
| | - Ernie Marshall
- The Clatterbridge Centre NHS Foundation Trust, Liverpool, UK
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Schremser K, Rogowski WH, Adler-Reichel S, Tufman ALH, Huber RM, Stollenwerk B. Cost-Effectiveness of an Individualized First-Line Treatment Strategy Offering Erlotinib Based on EGFR Mutation Testing in Advanced Lung Adenocarcinoma Patients in Germany. PHARMACOECONOMICS 2015; 33:1215-1228. [PMID: 26081300 DOI: 10.1007/s40273-015-0305-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
BACKGROUND Lung cancer is among the top causes of cancer-related deaths. Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors can increase progression-free survival compared with standard chemotherapy in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). OBJECTIVE The aim of the study was to evaluate the cost-effectiveness of EGFR mutation analysis and first-line therapy with erlotinib for mutation-positive patients compared with non-individualized standard chemotherapy from the perspective of German statutory health insurance. METHODS A state transition model was developed for a time horizon of 10 years (reference year 2014). Data sources were published data from the European Tarceva versus Chemotherapy (EURTAC) randomized trial for drug efficacy and safety and German cost data. We additionally performed deterministic, probabilistic and structural sensitivity analyses. RESULTS The individualized strategy incurred 0.013 additional quality-adjusted life-years (QALYs) and additional costs of € 200, yielding an incremental cost-effectiveness ratio (ICER) of € 15,577/QALY. Results were most sensitive to uncertainty in survival curves and changes in utility values. Cross-validating health utility estimates with recent German data increased the ICER to about € 58,000/QALY. The probabilistic sensitivity analysis indicated that the individualized strategy is cost-effective, with a probability exceeding 50 % for a range of possible willingness-to-pay thresholds. LIMITATIONS The uncertainty of the predicted survival curves is substantial, particularly for overall survival, which was not a primary endpoint in the EURTAC study. Also, there is limited data on quality of life in metastatic lung cancer patients. CONCLUSIONS Individualized therapy based on EGFR mutation status has the potential to provide a cost-effective alternative to non-individualized care for patients with advanced adenocarcinoma. Further clinical research is needed to confirm these results.
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Affiliation(s)
- Katharina Schremser
- Helmholtz Zentrum München (GmbH), German Research Center for Environmental Health (GmbH), Institute of Health Economics and Health Care Management, Member of the German Center for Lung Research, Comprehensive Pneumology Center Munich (CPC-M), Ingolstädter Landstraße 1, 85758, Neuherberg, Germany.
| | - Wolf H Rogowski
- Helmholtz Zentrum München (GmbH), German Research Center for Environmental Health (GmbH), Institute of Health Economics and Health Care Management, Member of the German Center for Lung Research, Comprehensive Pneumology Center Munich (CPC-M), Ingolstädter Landstraße 1, 85758, Neuherberg, Germany
- Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Clinical Center, University of Munich, Munich, Germany
| | - Sigrid Adler-Reichel
- Division of Hematology and Oncology, Medical Clinic and Policlinic IV, University of Munich, Munich, Germany
| | - Amanda L H Tufman
- Division of Respiratory Medicine and Thoracic Oncology, Medical Clinic and Policlinic V, Thoracic Oncology Centre Munich, University of Munich, Member of the German Center for Lung Research, Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany
| | - Rudolf M Huber
- Division of Respiratory Medicine and Thoracic Oncology, Medical Clinic and Policlinic V, Thoracic Oncology Centre Munich, University of Munich, Member of the German Center for Lung Research, Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany
| | - Björn Stollenwerk
- Helmholtz Zentrum München (GmbH), German Research Center for Environmental Health (GmbH), Institute of Health Economics and Health Care Management, Member of the German Center for Lung Research, Comprehensive Pneumology Center Munich (CPC-M), Ingolstädter Landstraße 1, 85758, Neuherberg, Germany
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20
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Inhibition of microRNA-196a might reverse cisplatin resistance of A549/DDP non-small-cell lung cancer cell line. Tumour Biol 2015; 37:2387-94. [PMID: 26376998 DOI: 10.1007/s13277-015-4017-7] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 08/28/2015] [Indexed: 01/05/2023] Open
Abstract
We aimed to explore the possible mechanism of microRNA-196a (miR-196a) inhibition and reversion of drug resistance to cisplatin (DDP) of the A549/DDP non-small-cell lung cancer (NSCLC) cell line. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect expression differences of miR-196a in the drug-resistant A549/DDP NLCLC cell line and the parental A549 cell line, and expressions of miR-196a in the A549/DDP NLCLC cell line transfected with miR-196a inhibitor (anti-miR-196a group) and the miR-196a negative control (miR-NC) group and blank group (without transfection). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was applied in examining the cell viability of A549/DDP cell line before and after transfection. Clonogenic assay was used to detect cell proliferation ability. Flow cytometry was applied in detecting apoptosis rate of assayed tumor cell and rhodamine-123 changes in cells. Western blot was applied in detecting proteins of drug-resistant related gene in A549/DDP cell line. Significantly higher expression of miR-196a was detected in the drug-resistant A549/DDP cell line than that in the parental A549 cell line (P < 0.05). However, miR-196a expression in the anti-miR-196a group decreased obviously compared to that in the blank group and the miR-NC group (both P < 0.05); The value of IC50 in the anti-miR-196a group showed remarkably lower than that in the blank group and the miR-NC group (both P < 0.05); Rh-123 absorbing ability in the anti-miR-196a group increased 2.51 times and 2.49 times respectively compared to that in the blank group and the miR-NC group (both P < 0.05). No statistical differences in the apoptosis rate of A549/DDP cell line in the early stage were found among the three groups (all P > 0.05), but the late-stage apoptosis rate in the anti-miR-196a group was significantly higher than that in the blank group and the miR-NC group (both P < 0.05); The expressions of human multidrug resistance 1 (MDR1), multidrug resistance protein 1 (MRP1), excision repair cross-complementation 1 (ERCC1), survivin, and B cell lymphoma 2 (Bcl-2) decreased significantly while RhoE increased significantly in the anti-miR-196a group than the blank group and the miR-NC group (all P < 0.05). Inhibition of miR-196a could reverse cisplatin resistance of A549/DDP cell lines, which might relate with inhibition of drug efflux, down-regulation of drug-resistant protein expression, cell apoptosis, and cell proliferation suppression.
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21
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Brown T, Pilkington G, Bagust A, Boland A, Oyee J, Tudur Smith C, Blundell M, Lai M, Martin Saborido C, Greenhalgh J, Dundar Y, Dickson R. Corrigendum: Clinical effectiveness and cost-effectiveness of first-line chemotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer: a systematic review and economic evaluation. Health Technol Assess 2015; 17:281-2. [PMID: 26061626 PMCID: PMC11345656 DOI: 10.3310/hta17310-c201505] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
AbstractTable 96 has been removed as it includes incorrect hazard ratios caused by a reversal of the hazard ratio calculations. However, this does not impact on any of the clinical or economic results reported.
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Affiliation(s)
- T Brown
- Liverpool Reviews and Implementation Group (LRiG), Institute of Psychology, Health and Society, Department of Health Services Research, University of Liverpool, Liverpool, UK
| | - G Pilkington
- Liverpool Reviews and Implementation Group (LRiG), Institute of Psychology, Health and Society, Department of Health Services Research, University of Liverpool, Liverpool, UK
| | - A Bagust
- Liverpool Reviews and Implementation Group (LRiG), Institute of Psychology, Health and Society, Department of Health Services Research, University of Liverpool, Liverpool, UK
| | - A Boland
- Liverpool Reviews and Implementation Group (LRiG), Institute of Psychology, Health and Society, Department of Health Services Research, University of Liverpool, Liverpool, UK
| | - J Oyee
- Liverpool Reviews and Implementation Group (LRiG), Institute of Psychology, Health and Society, Department of Health Services Research, University of Liverpool, Liverpool, UK
| | - C Tudur Smith
- Department of Biostatistics, University of Liverpool, Liverpool, UK
| | - M Blundell
- Liverpool Reviews and Implementation Group (LRiG), Institute of Psychology, Health and Society, Department of Health Services Research, University of Liverpool, Liverpool, UK
| | - M Lai
- Liverpool Reviews and Implementation Group (LRiG), Institute of Psychology, Health and Society, Department of Health Services Research, University of Liverpool, Liverpool, UK
| | - C Martin Saborido
- Liverpool Reviews and Implementation Group (LRiG), Institute of Psychology, Health and Society, Department of Health Services Research, University of Liverpool, Liverpool, UK
| | - J Greenhalgh
- Liverpool Reviews and Implementation Group (LRiG), Institute of Psychology, Health and Society, Department of Health Services Research, University of Liverpool, Liverpool, UK
| | - Y Dundar
- Liverpool Reviews and Implementation Group (LRiG), Institute of Psychology, Health and Society, Department of Health Services Research, University of Liverpool, Liverpool, UK
| | - R Dickson
- Liverpool Reviews and Implementation Group (LRiG), Institute of Psychology, Health and Society, Department of Health Services Research, University of Liverpool, Liverpool, UK
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Loveman E, Copley VR, Colquitt J, Scott DA, Clegg A, Jones J, O’Reilly KMA, Singh S, Bausewein C, Wells A. Corrigendum. Health Technol Assess 2015. [DOI: 10.3310/hta17310-c201311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
SummaryA previous version of this report was published in July 2013. The report was corrected on page v in November 2013. For further information, or for copies of the original material, please contact Nihredit@soton.ac.uk.
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Affiliation(s)
- Emma Loveman
- Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK
| | - Vicky R Copley
- Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK
| | - Jill Colquitt
- Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK
| | | | - Andy Clegg
- Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK
| | - Jeremy Jones
- Southampton Health Technology Assessments Centre, University of Southampton, Southampton, UK
| | - Katherine MA O’Reilly
- Department of Respiratory Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Sally Singh
- Cardiac and Pulmonary Rehabilitation, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Claudia Bausewein
- Department of Palliative Medicine, University Hospital of Munich, Munich, Germany
| | - Athol Wells
- Interstitial Lung Disease Unit, Royal Brompton and Harefield NHS Trust, London, UK
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23
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Chouaïd C, Crequit P, Borget I, Vergnenegre A. Economic evaluation of first-line and maintenance treatments for advanced non-small cell lung cancer: a systematic review. CLINICOECONOMICS AND OUTCOMES RESEARCH 2014; 7:9-15. [PMID: 25548525 PMCID: PMC4271788 DOI: 10.2147/ceor.s43328] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
During these last years, there have been an increased number of new drugs for non-small cell lung cancer (NSCLC), with a growing financial effect on patients and society. The purpose of this article was to review the economics of first-line and maintenance NSCLC treatments. We reviewed economic analyses of NSCLC therapies published between 2004 and 2014. In first-line settings, in unselected patients with advanced NSCLC, the cisplatin gemcitabine doublet appears to be cost-saving compared with other platinum doublets. In patients with nonsquamous NSCLC, the incremental cost-effectiveness ratios (ICERs) per life-year gained (LYG) were $83,537, $178,613, and more than $300,000 for cisplatin-pemetrexed compared with, respectively, cisplatin-gemcitabine, cisplatin-carboplatin-paclitaxel, and carboplatin-paclitaxel-bevacizumab. For all primary chemotherapy agents, use of carboplatin is associated with slightly higher costs than cisplatin. In all the analysis, bevacizumab had an ICER greater than $150,000 per quality-adjusted life-year (QALY). In epidermal growth factor receptor mutated advanced NSCLC, compared with carboplatin-paclitaxel doublet, targeted therapy based on testing available tissue yielded an ICER of $110,644 per QALY, and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Compared with the triplet carboplatin-paclitaxel-bevacizumab, testing and rebiopsy strategies had ICERs of $25,547 and $44,036 per QALY, respectively. In an indirect comparison, ICERs per LYG and QALY of erlotinib versus gefitinib were $39,431 and $62,419, respectively. In anaplastic lymphoma kinase-positive nonsquamous advanced NSCLC, the ICER of first-line crizotinib compared with that of chemotherapy was $255,970 per QALY. For maintenance therapy, gefitinib had an ICER of $19,214 per QALY, erlotinib had an ICER of $127,343 per LYG, and pemetrexed had an ICER varying between $183,589 and $205,597 per LYG. Most recent NSCLC strategies are based on apparently no cost-effective strategies if we consider an ICER below $50,000 per QALY an acceptable threshold. We need, probably on a countrywide level, to have a debate involving public health organizations and pharmaceutical companies, as well as clinicians and patients, to challenge the rising costs of managing lung cancer.
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Affiliation(s)
- Christos Chouaïd
- Service de Pneumologie et de Pathologie Professionnelle, Centre Hospitalier Intercommunal Créteil et Université de Paris Est Créteil, Paris, France
| | - Perinne Crequit
- Service de Pneumologie, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Isabelle Borget
- Service de Biostatistique et d'Epidémiologie, Institut Gustave Roussy, Villejuif, France
| | - Alain Vergnenegre
- Unité d'Oncologie Thoracique et Cutanée, Centre Hospitalier Universitaire Limoges, Limoges, France
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Lim C, Sergi M, Leighl NB. Targeted therapy for lung cancer: reviewing the cost and its effect on treatment decisions. Lung Cancer Manag 2014. [DOI: 10.2217/lmt.14.36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
SUMMARY Novel targeted therapies that improve outcome in advanced lung cancer should be adopted. However, given the high costs of targeted therapies and companion molecular testing, the affordability and cost–effectiveness of novel agents are of growing relevance in policy decisions. Incremental cost–effectiveness ratios in excess of US$200,000 per quality-adjusted life year have been described in published literature evaluating currently approved agents. Differing willingness to pay thresholds in different countries determine which therapies will be funded in a given healthcare system. Cost-containment strategies to address costs of molecular testing and drug acquisition need to be implemented. Drug manufacturers, healthcare payers and oncologists have a shared responsibility to ensure that novel therapies are affordable and accessible to patients in need.
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Affiliation(s)
- Charles Lim
- Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada
- University of Toronto, Toronto, ON, Canada
| | - Melissa Sergi
- Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada
- University of Toronto, Toronto, ON, Canada
| | - Natasha B Leighl
- Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada
- University of Toronto, Toronto, ON, Canada
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Graham DM, Leighl NB. Economic Impact of Tissue Testing and Treatments of Metastatic NSCLC in the Era of Personalized Medicine. Front Oncol 2014; 4:258. [PMID: 25295228 PMCID: PMC4170132 DOI: 10.3389/fonc.2014.00258] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Accepted: 09/05/2014] [Indexed: 01/11/2023] Open
Abstract
A paradigm-shift in the management of non-small cell lung cancer (NSCLC) has resulted in many new therapies becoming available for patients with advanced disease. Stratification of treatment by histologic and molecular subtype is recommended to obtain the greatest clinical benefit for patients while minimizing adverse effects of treatment. However, these advances in diagnosis and treatment of NSCLC have come at a financial cost. This review highlights the economic impact of screening for molecular abnormalities and targeted treatment for advanced NSCLC. Major determinants of cost are drug acquisition and molecular testing. As technologies advance, molecular testing costs may reduce. However, we must collaborate with payers and manufacturers to ensure that high drug costs do not limit patient accessibility to potentially beneficial treatment.
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Affiliation(s)
- Donna M. Graham
- Department of Medicine, Division of Hematology and Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - Natasha B. Leighl
- Department of Medicine, Division of Hematology and Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
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Miceli R, Tomasello G, Bregni G, Bartolomeo MD, Pietrantonio F. Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges. World J Gastroenterol 2014; 20:4516-4525. [PMID: 24782604 PMCID: PMC4000488 DOI: 10.3748/wjg.v20.i16.4516] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2013] [Revised: 01/09/2014] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that disease-free survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment.
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