Abstract
Introduction: In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in patients with previously treated, advanced NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% and ≥1%. We report 5-year efficacy and safety follow-up for the KEYNOTE-010 study. Methods: Patients were randomized to pembrolizumab 2 mg/kg or 10 mg/kg once every 3 weeks or docetaxel 75 mg/m2 once every 3 weeks for up to 35 cycles (2 y). Patients who completed pembrolizumab treatment and subsequently had recurrence could receive second-course pembrolizumab for up to 17 cycles (1 y). Pembrolizumab doses were pooled in this analysis. Results: A total of 1034 patients were randomized (pembrolizumab, n = 691; docetaxel, n = 343). Median study follow-up was 67.4 months (range: 60.0‒77.9). The hazard ratio (95% confidence interval) for OS was 0.55 (0.44‒0.69) for patients with PD-L1 TPS ≥50% and 0.70 (0.61‒0.80) with PD-L1 TPS ≥1%. The 5-year OS rates for pembrolizumab versus docetaxel were 25.0% versus 8.2% in patients with PD-L1 TPS ≥50% and 15.6% versus 6.5% with PD-L1 TPS ≥1%. Among 79 patients who completed 35 cycles/2 years of pembrolizumab, the OS rate 3 years after completion (∼5 y from randomization) was 83.0%. A total of 21 patients received second-course pembrolizumab; 11 (52.4%) had an objective response after starting the second course and 15 (71.4%) were alive at data cutoff. Exploratory biomarker analysis revealed that higher tissue tumor mutational burden (≥175 mutations per exome) was associated with improved outcomes with pembrolizumab. Conclusions: Pembrolizumab continued to provide long-term benefit than docetaxel in patients with previously treated advanced NSCLC with PD-L1 TPS ≥50% and ≥1%. Our findings confirm pembrolizumab as a standard-of-care treatment in the second-line or later setting.
| Original language | English |
|---|---|
| Pages (from-to) | 1718-1732 |
| Number of pages | 15 |
| Journal | Journal of Thoracic Oncology |
| Volume | 16 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2021 Oct |
Bibliographical note
Funding Information:Funding for this research was provided by Merck Sharp & Dohme Corp. , a subsidiary of Merck & Co., Inc. , Kenilworth, NJ, USA. Representatives of the funder participated in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Medical writing assistance was provided by Christabel Wilson, MSc, of ICON plc (North Wales, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp. , a subsidiary of Merck & Co., Inc. , Kenilworth, NJ, USA.
Funding Information:
Disclosure: Prof. Herbst reports having commercial research grants from AstraZeneca, Eli Lilly, and Merck; serving as consultant/advisory board member for AbbVie, AstraZeneca, Biodesix, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Genentech/Roche, Heat Biologics, Infinity Pharmaceuticals, Loxo Oncology, Merck, Nektar Therapeutics, Neon Therapeutics, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire, Spectrum Pharmaceuticals, Symphogen, Tesaro, ARMO BioSciences, Genmab, and Tocagen; and serving as board member (nonexecutive/independent) for Junshi Biosciences and Immunocore (nonexecutive director). Dr. Garon reports having research grants from Novartis, Merck, EMD Serono, Bristol-Myers Squibb, Eli Lilly, Genentech, AstraZeneca, Dynavax Technologies, Iovance Biotherapeutics, and Mirati Therapeutics; receiving honoraria/fees from ABL-Bio, Xilio, Shionogi, Sanofi, Novartis, Natera, Merck, GlaxoSmithKline, Eisai, EMD Serono, Dracen Pharmaceuticals, Boehringer Ingelheim, and Bristol-Myers Squibb. Dr. Kim reports receiving research funding to institution from Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer Ingelheim, Daiichi Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, Merck Sharp & Dohme, Novartis, Ono Pharmaceuticals, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan; and receiving travel and accommodation support for advisory board meeting attendance from Amgen and Daiichi Sankyo. Dr. Cho reports receiving research grants and support from Novartis, Bayer, AstraZeneca, Mogam Biotechnology Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono Pharmaceuticals, Dizal Pharma, Merck Sharp & Dohme, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, and Interpark Bio Convergence Corp; being on consulting or advisory boards for Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Ono Pharmaceuticals, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, Merck Sharp & Dohme, Medpacto, Blueprint Medicines, KANAPH Therapeutic Inc., Brigebio Therapeutics, Cyrus Therapeutics, Guardant Health, and Oscotec Inc.; having stock ownership for TheraCanVac Inc., Gencurix Inc., BridgeBio Inc., KANAPH Therapeutic Inc., Cyrus Therapeutics, and Interpark Bio Convergence Corp; serving on board of directors of Gencurix Inc. and Interpark Bio Convergence Corp; having royalty from Champions Oncology; and being a founder of DAAN Biotherapeutics. Dr. Gervais reports receiving support from Merck Sharp & Dohme, Bristol-Myers Squibb, Roche, and AstraZeneca for meetings and advisory boards. Dr. Perez-Gracia reports receiving research grants and support from Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, Ipsen, Eisai, Incyte, Janssen, and Seattle Genetics; being on speakers bureau and advisory boards for Roche, Bristol-Myers Squibb, Ipsen, Eisai, and Merck Sharp & Dohme; and receiving travel support from Roche, Merck Sharp & Dohme, and Bristol-Myers Squibb. Dr. Han reports receiving honoraria from Roche, AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, and Takeda; having advisory role for AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Eli Lilly, Novartis, Pfizer, and Takeda; and receiving research grants from Roche, Pfizer, and Ono Pharmaceuticals. Dr. Majem reports receiving research grant from Bristol-Myers Squibb; having advisory role and receiving honoraria from AstraZeneca, Roche, Eli Lilly, Bristol-Myers Squibb, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Pfizer, Boehringer Ingelheim, Novartis, Helsinn, Pierre Fabre, Kyowa Kyrin, and Takeda; and receiving travel support from Boehringer Ingelheim and Eli Lilly. Dr. Forster reports having research grants from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Daiichi Sankyo, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; having advisory roles and receiving honoraria from Achilles, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardant, Merck, Merck Sharp & Dohme, Nanobiotix, Novartis, Pfizer, PharmaMar, Roche, and Takeda; and receiving support from the UCL/UCLH NIHR Biomedical Research Centre. Dr. Monnet reports receiving travel support from Roche, AstraZeneca, Pfizer, Merck Sharp & Dohme, and Bristol-Myers Squibb. Dr. Novello reports being on speakers bureau/advisor for AMG, AstraZeneca, AbbVie, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Celgene, Bristol-Myers Squibb, Takeda, Pfizer, Sanofi, Beigene, Janssen, Novartis, and Roche. Dr. Gubens reports serving as consultant for AstraZeneca, BeyondSpring, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech/Roche, Heron Therapeutics, and Takeda; and receiving research support to institution from Celgene, Merck, Novartis, OncoMed, and Roche. Dr. Boyer reports receiving grants and nonfinancial support from Merck Sharp & Dohme during the conduct of this study; grants and nonfinancial support from AstraZeneca, Bristol-Myers Squibb, Janssen, and Genentech/Roche; and grants from Amgen, Pfizer, Eli Lilly, and Novartis. Dr. Jensen reports being an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Drs. Samkari, Kobie, and Piperdi report being employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and owning stock in Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Dr. Baas reports receiving research grants from and serving as advisory board member for Bristol-Myers Squibb and Merck Sharp & Dohme; and serving as advisory board member for Boehringer Ingelheim, Beigene, AstraZeneca, and Pfizer. Dr. Su declares no conflict of interest.Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. Representatives of the funder participated in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Medical writing assistance was provided by Christabel Wilson, MSc, of ICON plc (North Wales, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, New Jersey (MSD), is committed to providing qualified scientific researchers access to anonymized data and clinical study reports from the company's clinical trials for the purpose of conducting legitimate scientific research. MSD is also obligated to protect the rights and privacy of trial participants and, as such, has a procedure in place for evaluating and fulfilling requests for sharing company clinical trial data with qualified external scientific researchers. The MSD data-sharing website (available at: http://engagezone.msd.com/ds_documentation.php) outlines the process and requirements for submitting a data request. Applications will be promptly assessed for completeness and policy compliance. Feasible requests will be reviewed by a committee of MSD subject matter experts to evaluate the scientific validity of the request and the qualifications of the requestors. In line with data privacy legislation, submitters of approved requests must enter into a standard data-sharing agreement with MSD before data access is granted. Data will be made available for request after product approval in the US and EU or after product development is discontinued. There are circumstances that may prevent MSD from sharing requested data, including country- or region-specific regulations. If the request is declined, it will be communicated to the investigator. Access to genetic or exploratory biomarker data requires a detailed, hypothesis-driven statistical analysis plan that is collaboratively developed by the requestor and MSD subject matter experts; after approval of the statistical analysis plan and execution of a data sharing agreement, MSD will either perform the proposed analyses and share the results with the requestor or will construct biomarker covariates and add them to a file with clinical data that is uploaded to an analysis portal so that the requestor can perform the proposed analyses.
Publisher Copyright:
© 2021
All Science Journal Classification (ASJC) codes
- Oncology
- Pulmonary and Respiratory Medicine