@article{921480a4146e4253a434309603a8df77,
title = "Outcomes With Pembrolizumab Monotherapy in Patients With Programmed Death-Ligand 1–Positive NSCLC With Brain Metastases: Pooled Analysis of KEYNOTE-001, 010, 024, and 042",
abstract = "Introduction: We retrospectively evaluated outcomes in patients with programmed death-ligand 1 (PD-L1)–positive NSCLC to determine whether baseline (i.e., at study enrollment) brain metastases were associated with the efficacy of pembrolizumab versus chemotherapy. Methods: We pooled the data for patients with previously treated or untreated PD-L1‒positive (tumor proportion score [TPS], ≥1%) advanced metastatic NSCLC in KEYNOTE-001 (NCT01295827), KEYNOTE-010 (NCT01905657), KEYNOTE-024 (NCT02142738), and KEYNOTE-042 (NCT02220894). Patients received pembrolizumab (2 mg/kg, 10 mg/kg, or 200 mg every 3 wk or 10 mg/kg every 2 wk); chemotherapy was a comparator in all studies except KEYNOTE-001. All studies included patients with previously treated, stable brain metastases. Results: A total of 3170 patients were included, 293 (9.2%) with and 2877 (90.8%) without baseline brain metastases; median (range) follow-up at data cutoff was 12.9 (0.1‒43.7) months. Pembrolizumab improved overall survival versus chemotherapy in patients with or without baseline brain metastases: benefit was seen in patients with PD-L1 TPS greater than or equal to 50% (0.67 [95% confidence intervals (CI): 0.44‒1.02] and 0.66 [95% CI: 0.58‒0.76], respectively) and PD-L1 TPS ≥1% (0.83 [95% CI: 0.62‒1.10] and 0.78 [95% CI: 0.71‒0.85], respectively). Progression-free survival was improved, objective response rates were higher, and the duration of response was longer with pembrolizumab versus chemotherapy regardless of brain metastasis status. The incidence of treatment-related adverse events with pembrolizumab versus chemotherapy was 66.3% versus 84.4% in patients with brain metastases and 67.2% versus 88.3% in those without. Conclusions: Pembrolizumab monotherapy improved outcomes and was associated with fewer adverse events than chemotherapy in patients with treatment-naive and previously treated PD-L1‒positive advanced/metastatic NSCLC regardless of the presence of baseline treated, stable brain metastases.",
keywords = "Brain metastases, Chemotherapy, Non‒small-cell lung cancer, PD-L1, Pembrolizumab",
author = "Mansfield, {Aaron S.} and Herbst, {Roy S.} and {de Castro}, Gilberto and Rina Hui and Nir Peled and Kim, {Dong Wan} and Silvia Novello and Miyako Satouchi and Wu, {Yi Long} and Garon, {Edward B.} and Martin Reck and Robinson, {Andrew G.} and Ayman Samkari and Bilal Piperdi and Victoria Ebiana and Jianxin Lin and Mok, {Tony S.K.}",
note = "Funding Information: Disclosure: Dr. Mansfield reports receiving honorarium on behalf of his institution from AstraZeneca, AbbVie, Bristol-Myers Squibb, and Genentech; research funding from National Institutes of Health, Novartis, and Verily; medical society/research group/foundation leadership that were not remunerated; and is a Mesothelioma Applied Research Foundation board member. Dr. Herbst reports receiving commercial research grants from AstraZeneca, Eli Lilly, and Merck; is a 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 is a board member (nonexecutive/independent) for Junshi Biosciences. Dr. Castro, Jr. reports receiving honoraria from Merck Sharp & Dohme, Bristol-Myers Squibb, Roche, Bayer, Novartis, Boehringer Ingelheim, AstraZeneca, and Pfizer; has an advisory/consultancy role for AstraZeneca, Merck Sharp & Dohme, Bristol-Myers Squibb, Roche, Novartis, Boehringer Ingelheim, Pfizer, Bayer, Merck Serono, and Yuhan; provides speakers bureau/expert testimony for Merck Sharp & Dohme, Bristol-Myers Squibb, Novartis, AstraZeneca, Pfizer, Roche, Bayer, and TEVA; receives research grant/funding on behalf of his institution from Merck Sharp & Dohme, Bristol-Myers Squibb, Roche, Novartis, Boehringer Ingelheim, AstraZeneca, Pfizer, and Merck Serono; and receives personal fees for travel/accommodation/expenses from Merck Sharp & Dohme, Bristol-Myers Squibb, Roche, Bayer, Novartis, Boehringer Ingelheim, AstraZeneca, and Pfizer. Dr. Hui reports receiving personal fees for advisory boards for Merck Sharp & Dohme, AstraZeneca, Novartis, Roche, and Bristol-Myers Squibb; and speaker honoraria from Merck Sharp & Dohme, Novartis, and Bristol-Myers Squibb. Dr. Peled reports receiving grants, personal fees, and honoraria for serving as an advisor for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, NovellusDx, FMI, and Gaurdant360. Dr. Kim reports receiving research funding on behalf of his institution from Alpha Biopharma, AstraZeneca/Medimmune, Hanmi, Janssen, Merus, Mirati Therapeutics, Merck Sharp & Dohme, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, XCovery, and Yuhan. Dr. Novello reports being a member of the speakers{\textquoteright} bureau/advisor for AstraZeneca, Boehringer Ingelheim, Celgene, AbbVie, Bristol-Myers Squibb, Eli Lilly, Pfizer, Takeda, Roche, and Merck Sharp & Dohme. Dr. Satouchi reports receiving honoraria from Merck Sharp & Dohme, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, AstraZeneca, Taiho Pharmaceutical, Pfizer, Novartis, Eli Lilly, Boehringer Ingelheim; and grants from Merck Sharp & Dohme, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, AstraZeneca, and Pfizer. Dr. Wu reports receiving honoraria from AstraZeneca, Eli Lilly, Roche, Pierre Fabre, Pfizer, and Sanofi; consulting or advisory role with AstraZeneca, Roche, Merck, and Boehringer Ingelheim; and research funding to the institution from Boehringer Ingelheim and Roche. Dr. Garon reports serving as advisory/consultancy role for Dracen, EMD Serono, and Merck; and receiving research funding on behalf of his institution from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Genentech, Neon Therapeutics, Iovance Biotherapeutics, Dynavax, and Mirati Therapeutics. Dr. Reck reports receiving honoraria for consulting and lectures for Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Merck, Merck Sharp & Dohme, Eli Lilly, Pfizer, AbbVie, Roche, and Novartis; speakers bureau and advisory board member for Amgen, AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Merck Sharp & Dohme, Merck, Novartis, Pfizer, and Roche; and receiving research grant to his institution from Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc. Dr. Robinson reports receiving grants from Bristol-Myers Squibb, Merck, Roche, and AstraZeneca. Drs. Samkari and Lin are employees 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 and owns stock in Merck & Co., Inc., Kenilworth, New Jersey. Dr. Ebiana was a former employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey. Dr. Mok reports receiving grants or research support from AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Merck Sharp & Dohme, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, and XCovery; speakers fees from AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Bristol-Myers Squibb, Taiho, and Takeda Oncology; honoraria from AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Merck Serono, Merck Sharp & Dohme, Novartis, SFJ Pharmaceuticals, ACEA Biosciences, Inc., Vertex Pharmaceuticals, Bristol-Myers Squibb, OncoGenex Pharmaceuticals, Inc., Celgene, Ignyta, Inc., Fishawack Facilitate Ltd., Takeda Oncology, and Janssen; is a major stockholder in Sanomics Ltd.; and is an advisory board member for AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Clovis Oncology, Merck Serono, Merck Sharp & Dohme, Novartis, SFJ Pharmaceuticals, ACEA Biosciences, Inc., Vertex Pharmaceuticals, Bristol-Myers Squibb, geneDecode Co., Ltd., OncoGenex Technologies Inc., Celgene, Ignyta, Inc., Cirina, Fishawack Facilitate Ltd., Janssen, Takeda, and ChiMed.Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc. Kenilworth, New Jersey. Representatives of the funder participated in study design, analysis, and interpretation of the data and supported the decision to submit the article for publication. Medical writing and editorial assistance were provided by Jennifer L. Venzie of ICON plc (North Wales, PA), funded by Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc., Kenilworth, New Jersey. Funding Information: Funding for this research was provided by Merck Sharp & Dohme Corp. , a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey. Representatives of the funder participated in study design, analysis, and interpretation of the data and supported the decision to submit the article for publication. Medical writing and editorial assistance were provided by Jennifer L. Venzie of ICON plc (North Wales, PA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. , Kenilworth, New Jersey. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = aug,
doi = "10.1016/j.jtocrr.2021.100205",
language = "English (US)",
volume = "2",
journal = "JTO Clinical and Research Reports",
issn = "2666-3643",
publisher = "Elsevier Inc.",
number = "8",
}