@article{ded0d2a640cd45c3a6c7d5cd65291d62,
title = "Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC",
abstract = "Introduction: In cohort G of KEYNOTE-021 (NCT02039674), first-line pembrolizumab plus pemetrexed-carboplatin significantly improved the objective response rate and progression-free survival versus chemotherapy alone with manageable toxicity in advanced nonsquamous NSCLC. We report the long-term outcomes from this study. Methods: Patients with previously untreated advanced nonsquamous NSCLC without sensitizing EGFR or ALK alterations were randomly assigned 1:1 to receive open-label pemetrexed 500 mg/m2 plus carboplatin at area under the concentration-time curve of 5 mg/mL/min (four cycles) with or without pembrolizumab 200 mg (up to 2 years), with optional pemetrexed maintenance, each administered every 3 weeks. Eligible patients could crossover from the chemotherapy arm to pembrolizumab monotherapy after progression. Responses were assessed per the Response Evaluation Criteria in Solid Tumors version 1.1. Results: After the median time of 49.4 months from randomization to data cutoff, objective response rate (58% versus 33%) and progression-free survival (median: 24.5 versus 9.9 mo; hazard ratio: 0.54; 95% confidence interval: 0.35‒0.83) remained improved with pembrolizumab combination (n = 60) versus chemotherapy (n = 63), regardless of programmed death ligand 1 status. Median overall survival was 34.5 versus 21.1 months (hazard ratio: 0.71; 95% confidence interval: 0.45‒1.12), despite a 70% crossover rate from chemotherapy alone to anti‒programmed death (ligand) 1 therapy. Among the 12 patients who completed 2 years of pembrolizumab, 92% were alive at data cutoff; the estimated 3-year duration of response rate was 100%. Grade 3 to 5 treatment-related adverse events occurred in 39% of patients receiving pembrolizumab combination and 31% receiving chemotherapy. Conclusions: First-line pembrolizumab plus pemetrexed-carboplatin continued to show improved response and survival versus chemotherapy alone in advanced nonsquamous NSCLC, with durable clinical benefit in patients who completed 2 years of therapy. No new safety signals were observed with longer follow-up.",
keywords = "Advanced nonsquamous non‒small-cell lung cancer, Chemotherapy, First-line therapy, Long-term survival, Pembrolizumab",
author = "Awad, {Mark M.} and Gadgeel, {Shirish M.} and Hossein Borghaei and Amita Patnaik and Yang, {James Chih Hsin} and Powell, {Steven F.} and Gentzler, {Ryan D.} and Martins, {Renato G.} and Stevenson, {James P.} and Mehmet Altan and Jalal, {Shadia I.} and Amit Panwalkar and Matthew Gubens and Sequist, {Lecia V.} and Sanatan Saraf and Bin Zhao and Bilal Piperdi and Langer, {Corey J.}",
note = "Funding Information: Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey. The study sponsor 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. The authors thank the patients, their families, and caregivers for participating in this study, along with all investigators and site personnel. The authors thank Eli Lilly and Company (Indianapolis, IN) for providing pemetrexed. Medical writing and editorial assistance were provided by Krystina Neuman, PhD, and Rozena Varghese, PharmD, CMPP, of ICON plc (North Wales, PA); this assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Drs. Awad, Gadgeel, Borghaei, Patnaik, Yang, Powell, Gentzler, Martins, Stevenson, Altan, Jalal, Panwalkar, Gubens, and Sequist contributed to the investigation, resources, writing—original draft, and writing—review and editing of the manuscript. Dr. Saraf contributed to formal analysis, writing—original draft, and writing—review and editing of the manuscript. Dr. Zhao contributed to writing—original draft, writing—review and editing, and supervision of the manuscript. Dr. Piperdi contributed to writing—original draft, writing—review and editing, visualization, and supervision of the manuscript. Dr. Langer contributed to investigation, resources, writing—original draft, and writing—review and editing of the manuscript. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey{\textquoteright}s data-sharing policy, including restrictions, is available at http://engagezone.msd.com/ds_documentation.php . Requests for access to the clinical study data can be submitted through the EngageZone site or by means of an e-mail to dataaccess@merck.com . Funding Information: Disclosure: Dr. Awad served as a consultant or served on the advisory boards of Bristol-Myers Squibb, AstraZeneca, Achilles Therapeutics, AbbVie, Neon Therapeutics, Maverick, Nektar Therapeutics, Hengrui Therapeutics, Syndax Pharmaceuticals, and Gritstone Oncology and received institutional research funding from Bristol-Myers Squibb, AstraZeneca, Eli Lilly, and Genentech. Dr. Gadgeel received personal fees from AstraZeneca, Genentech/Roche, Takeda Pharmaceuticals/Ariad, Boehringer Ingelheim, Novocure, Bristol-Myers Squibb, AbbVie, Xcovery, Merck, Novartis, Daiichi Sankyo, PharmaMar, and Loxo Oncology; received research support from Merck; and served on the Independent Data Monitoring Committee for AstraZeneca. Dr. Borghaei received research support from Millennium, Merck/Celgene, and Bristol-Myers Squibb/Eli Lilly; served on the advisory boards or in a consultant role for Bristol-Myers Squibb, Eli Lilly, Genentech, Celgene, Pfizer, Merck, EMD Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Cantargia AB, Amgen, AbbVie, Axiom, PharmaMar, Takeda Pharmaceuticals, Huya Bioscience, GLG Pharma, and Daiichi Sankyo; served as a data and safety monitoring board member for the University of Pennsylvania CAR T Program, Takeda Pharmaceuticals, and Incyte; and served on the advisory boards of Sonnetbio and Rgenix with stock options. Dr. Patnaik received institutional research funding from Merck. Dr. Yang received personal fees as an advisor for Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai Pharmaceuticals, Astellas, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, Merrimack, Yuhan Pharmaceutical, Bristol-Myers Squibb, Ono Pharmaceutical, and AstraZeneca. Dr. Powell received institutional grant support from Bristol-Myers Squibb, Genentech, Incyte, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, Pfizer, Novartis, Actuate, and Vyriad; and received institutional support for consulting from Bristol-Myers Squibb. Dr. Gentzler served in a consulting role for or received honoraria from AstraZeneca, BluePrint Medicines, and Pfizer; and received institutional research funding from Merck, Bristol-Myers Squibb, Takeda Pharmaceuticals, Pfizer, Jounce Therapeutics, and Helsinn. Dr. Stevenson received institutional research funding from Merck, EMD Serono, and Bristol-Myers Squibb; served as DSMB member for Trizell, Ltd.; and participated in scientific advisory boards for Novocure and United Healthcare. Dr. Altan received institutional research funding from Merck, Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Jounce Therapeutics, Adaptimmune, Nektar Therapeutics, and Genentech; and served on the advisory boards of Shattuck Labs and GlaxoSmithKline. Dr. Jalal received research funding from AstraZeneca, Tesaro, and Astex Pharmaceuticals. Dr. Panwalkar received institutional research funding from Merck. Dr. Gubens served in a consulting role for AstraZeneca, BeyondSpring Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech/Roche, Heron Therapeutics, and Takeda Pharmaceuticals; and received institutional research funding from Celgene, Merck, Novartis, OncoMed Pharmaceuticals, and Roche. Dr. Sequist received grant support from or served in a consulting role for AstraZeneca, Merrimack Pharmaceuticals, and Genentech; received grant support from Boehringer Ingelheim, Loxo Oncology, Blueprint Medicines, and Novartis; and served in a consulting role for Janssen. Dr. Saraf is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey. Dr. Zhao is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey. Dr. Piperdi is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey. Dr. Langer received grant or research support from Pfizer, Eli Lilly, Genentech, Merck, GlaxoSmithKline, Nektar Therapeutics, Advantage, Clovis Oncology, Inovio Pharmaceuticals, ARIAD Pharmaceuticals, Stemcentrx, Takeda, and Guardant Health; served as a scientific advisor for Merck, AbbVie, Bristol-Myers Squibb, Pfizer, Eli Lilly, AstraZeneca, Novartis, Roche/Genentech, Bayer/Onyx, Abbott, Morphotek, Biodesix, Clarient, Caris Diagnostics, Vertex, Synta Pharmaceuticals, Celgene, Boehringer Ingelheim, Hospira, Helsinn, Clovis, ARIAD Pharmaceuticals (Takeda Pharmaceuticals), Takai, Gilead, and Regeneron; served as a data and safety monitoring committee member for Eli Lilly, Amgen, Synta Pharmaceuticals, Agennix, SWOG, Peregrine Pharmaceuticals, and Incyte; and served as a continuing medical education presenter for PIK, PER, NOCR, Imedex, CCO, RTP, MLG, TRM, and Web-MD. Dr. Martins declares no conflict of interest.Funding for this research was provided by Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, New Jersey. The study sponsor 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. The authors thank the patients, their families, and caregivers for participating in this study, along with all investigators and site personnel. The authors thank Eli Lilly and Company (Indianapolis, IN) for providing pemetrexed. Medical writing and editorial assistance were provided by Krystina Neuman, PhD, and Rozena Varghese, PharmD, CMPP, of ICON plc (North Wales, PA); this assistance was funded by Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA. Drs. Awad, Gadgeel, Borghaei, Patnaik, Yang, Powell, Gentzler, Martins, Stevenson, Altan, Jalal, Panwalkar, Gubens, and Sequist contributed to the investigation, resources, writing—original draft, and writing—review and editing of the manuscript. Dr. Saraf contributed to formal analysis, writing—original draft, and writing—review and editing of the manuscript. Dr. Zhao contributed to writing—original draft, writing—review and editing, and supervision of the manuscript. Dr. Piperdi contributed to writing—original draft, writing—review and editing, visualization, and supervision of the manuscript. Dr. Langer contributed to investigation, resources, writing—original draft, and writing—review and editing of the manuscript. Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, New Jersey's data-sharing policy, including restrictions, is available at http://engagezone.msd.com/ds_documentation.php. Requests for access to the clinical study data can be submitted through the EngageZone site or by means of an e-mail to dataaccess@merck.com. Publisher Copyright: {\textcopyright} 2020 International Association for the Study of Lung Cancer",
year = "2021",
month = jan,
doi = "10.1016/j.jtho.2020.09.015",
language = "English (US)",
volume = "16",
pages = "162--168",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "1",
}
