Safety of pembrolizumab as adjuvant therapy in a pooled analysis of phase 3 clinical trials of melanoma, non-small cell lung cancer, and renal cell carcinoma.

Background: The safety profile of adjuvant pembrolizumab was evaluated in a pooled analysis of 4 phase 3 clinical trials.
Methods: Patients had completely resected stage IIIA, IIIB, or IIIC melanoma per American Joint Committee on Cancer, 7th edition, criteria (AJCC-7; KEYNOTE-054); stage IIB or IIC melanoma per AJCC-8 (KEYNOTE-716); stage IB, II, or IIIA non-small cell lung cancer per AJCC-7 (PEARLS/KEYNOTE-091); or postnephrectomy/metastasectomy clear cell renal cell carcinoma at increased risk of recurrence (KEYNOTE-564). Patients received adjuvant pembrolizumab 200 mg (2 mg/kg up to 200 mg for pediatric patients) or placebo every 3 weeks for approximately 1 year. Adverse events (AEs) were summarized for patients who received ≥ 1 dose of treatment.
Results: Data were pooled from 4125 patients treated with pembrolizumab (n = 2060) or placebo (n = 2065). Median (range) duration of treatment was 11.1 months (0.0-18.9) with pembrolizumab and 11.2 months (0.0-18.1) with placebo. Treatment-related AEs occurred in 78.6 % (1620/2060) of patients in the pembrolizumab group (grade 3-5, 16.3 % [336/2060]) and 58.7 % (1212/2065) in the placebo group (grade 3-5, 3.5 % [72/2065]). Immune-mediated AEs (e.g. adrenal insufficiency, hypophysitis, and thyroiditis) occurred in 36.2 % (746/2060) of patients in the pembrolizumab group (grade 3-5, 8.6 % [177/2060]) and 8.4 % (174/2065) in the placebo group (grade 3-5, 1.1 % [23/2065]). Of patients with ≥ 1 immune-mediated AE or infusion reaction, systemic corticosteroids were required for 35.2 % (268/761) and 20.2 % (39/193) of patients in the pembrolizumab and placebo groups, respectively.
Conclusions: Adjuvant pembrolizumab demonstrated a manageable safety profile that was comparable to prior reports in advanced disease.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jason J. Luke reports grants or contracts from AbbVie, Astellas, AstraZeneca, Bristol Myers Squibb, Corvus, Day One, EMD Serono, Fstar, Genmab, Ikena, Immatics, Incyte, Kadmon, KAHR, Macrogenics, MSD, Moderna, Nektar, Next Cure, Numab, Palleon, Pfizer, Replimmune, Rubius, Servier, Scholar Rock, Synlogic, Takeda, Trishula, Tizona, and Xencor; consulting fees from 7 Hills, Bright Peak, Exo, Fstar, Inzen, RefleXion, Xilio, Actym, Alphamab Oncology, Arch Oncology, Duke Street Bio, Kanaph, Mavu, NeoTx, Onc.AI, OncoNano, Pyxis, Saros, STipe, Tempest, AbbVie, Alnylam, Atomwise, Bayer, Bristol Myers Squibb, Castle, Checkmate, Codiak, Crown, Cugene, Curadev, Day One, Eisai, EMD Serono, Endeavor, Flame, G1 Therapeutics, Genentech, Gilead, Glenmark, HotSpot, Kadmon, KSQ, Janssen, Ikena, Inzen, Immatics, Immunocore, Incyte, Instil, IO Biotech, Macrogenics, MSD, Mersana, Nektar, Novartis, Partner, Pfizer, Pioneering Medicines, PsiOxus, Regeneron, Ribon, Roivant, Servier, STINGthera, Synlogic, and Synthekine; patents planned, issued, or pending for Serial #15/612,657 (Cancer Immunotherapy) and PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof) (both provisional); participation in a Data Safety Monitoring Board or Advisory Board for AbbVie, Immutep, and Evaxion; a leadership or fiduciary role at the Society for Immunotherapy of Cancer; and stock or stock options in Actym, Alphamab Oncology, Arch Oncology, Duke Street Bio, Kanaph, Mavu, NeoTx, Onc.AI, OncoNano, Pyxis, Saros, STipe, and Tempest. Georgina V. Long reports consulting fees and participating on a Data Safety Monitoring Board or Advisory Board for Agenus Inc, Amgen Inc, Array Biopharma, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., Innovent Biologics USA Inc, MSD, Novartis Pharma AG, OncoSec Medical Australia, Pierre Fabre, Provectus Australia, Qbiotics Group Limited, and Regeneron Pharmaceuticals; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bristol Myers Squibb and Pierre Fabre. Caroline Robert reports support for medical writing for the present manuscript from MSD; consulting fees from BMS, Roche, MSD, Sanofi, Pierre Fabre, Sunpharma, Pfizer, and Regeneron; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from BMS, Pierre Fabre, and Sanofi; participation on a Data Safety Monitoring Board or Advisory Board from Ultimovacs and Regeneron; and stock or stock options in Ribonexus. Matteo S. Carlino reports consulting fees from Amgen, BMS, Eisai, Ideaya, MSD, Nektar, Novartis, Oncosec, Pierre Fabre, Qbiotics, Regeneron, Roche, SMD, and Sanofi; and honoraria for lectures from BMS, MSD, Novartis, Pierre Fabre, and Sanofi. Toni K. Choueiri reports support from Alkermes, AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVA, Infiniti, Ipsen, Kanaph, Lilly, MSD, Nikang, Novartis, Nuscan, Pfizer, Roche, Sanofi/Aventis, Surface Oncology, Takeda, Tempest, Up-To-Date, and CME events (Peerview, PER, MJH Life Sciences, Research to Practice, France Foundation, Springer, WebMed, ASiM Ce, Caribou Publishing, and others); grants or contracts from AstraZeneca, Aveo, Arcus, Bayer, Bristol Myers Squibb, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Lilly, MSD, Nikang, Novartis, Pfizer, Roche, Sanofi/Aventis, and Takeda; consulting fees from AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVIA, Infiniti, Ipsen, Kanaph, Lilly, MSD, Nikang, Novartis, Nuscan, Pfizer, Roche, Sanofi/Aventis, Surface Oncology, Takeda, Tempest, Up-To-Date, and CME events (Peerview, PER, MJH Life Sciences, Research to Practice, France Foundation, Springer, WebMed, ASiM Ce, Caribou Publishing); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVIA, Infiniti., Ipsen, Kanaph, Lilly, MSD, Nikang, Novartis, Pfizer, Roche, Sanofi/Aventis, Takeda, Tempest, Up-To-Date, CME events (Peerview, PER, MJH Life Sciences, Research to Practice, France Foundation, Springer, WebMed, ASiM Ce, Caribou Publishing); a patent planned, issued, or pending related to ctDNA and biomarkers of response to immune checkpoint inhibitors; participation in a Data Safety Monitoring Board or Advisory Board for Aravive; a leadership or fiduciary role with KidneyCan, ASCO, ESMO, NCCN, GU, and NCI; stock or stock options in Pionyr, Tempest, Precede Bio, Osel, Curesponse, Immdura, and Primium; and other financial or non-financial interests including support from the Dana-Farber/Harvard Cancer Center Kidney SPORE (2P50CA101942–16) and Program 5P30CA006516–56, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, Pan-Mass Challenge, Hinda and Arthur Marcus Fund and Loker Pinard Funds for Kidney Cancer Research at DFC. Naomi B. Haas reports participation on a data safety monitoring board or advisory board for MSD, Eisai, and Exelixis. Mary O’Brien reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca and MSD; support for attending ESMO from AstraZeneca; and participation on an IDMC. Luis Paz-Ares reports grants or contracts from MSD, AstraZeneca, BMS, Pfizer, and PharmaMar; consulting fees from Lilly, MSD, Roche, PharmaMar, AstraZeneca, Novartis, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda, and Regeneron; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Lilly, MSD, Roche, PharmaMar, AstraZeneca, Novartis, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda, and Regeneron; support for attending meetings and/or travel from Lilly, MSD, Roche, PharmaMar, AstraZeneca, Novartis, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda, and Regeneron; participation on a data safety monitoring board or advisory board for Altum Sequencing and Stab Therapeutics; and stock or stock options in Altum Sequencing and Stab Therapeutics. Solange Peters reports support for the present manuscript from MSD; grants or contracts from Amgen, Arcus, AstraZeneca, BeiGene, Bristol Myers Squibb, GSK, iTeos, MSD, Mirati, Pharma Mar, Promontory Therapeutics, Roche/Genentech, and Seattle Genetics; consulting fees from AbbVie, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, BerGenBio, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GSK, Hutchmed, Illumina, Incyte, Ipsen, iTeos, Janssen, MSD, Merrimack, Mirati, Nykode Therapeutics, Novartis, Novocure, Pharma Mar, Promontory Therapeutics, Pfizer, Regeneron, Roche/Genentech, Sanofi, Seattle Genetics, and Takeda; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Foundation Medicine, GSK, Illumina, Ipsen, MSD, Mirati, Novartis, Pfizer, Roche/Genentech, Sanofi, and Takeda; support for attending meetings and/or travel from AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pfizer, Roche/Genentech, and Takeda; participation on a Data Safety Monitoring Board or Advisory Board for AbbVie, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, BerGenBio, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GSK, Hutchmed, Illumina, Incyte, Ipsen, iTeos, Janssen, MSD, Merrimack, Mirati, Nykode Therapeutics, Novartis, Novocure, Pharma Mar, Promontory Therapeutics, Pfizer, Regeneron, Roche/Genentech, Sanofi, Seattle Genetics, and Takeda; and a leadership or fiduciary role with Galenica SA. Thomas Powles reports support for the present manuscript from Astellas and Open Health; grants or contracts from AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Ipsen, MSD, Novartis, Pfizer, Seattle Genetics, Astellas, Johnson & Johnson, and Eisai; consulting fees from AstraZeneca, Roche, Bristol Myers Squibb, Exelixis, Ipsen, MSD, Novartis, Pfizer, Seattle Genetics, Astellas, Johnson & Johnson, Eisai, and Mashup Ltd; and support for attending meetings and/or travel from Roche, Pfizer, MSD, AstraZeneca, and Ipsen. Melanie A. Leiby, Jianxin Lin, Clemens Krepler, Rodolfo F. Perini, M. Catherine Pietanza, Todd Gruber, and Nageatte Ibrahim report employment at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and stock ownership in Merck & Co., Inc., Rahway, NJ, USA. Ayman Samkari and Yujie Zhao reports employment at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Alexander M. M. Eggermont reports support for the present manuscript from Merck & Co; consulting fees from Alcetra, Agenus, BioInvent, Brenus, CatalYm, Ellipses, Epics, GSK, IO Biotech, IQVIA, ISA Pharmaceuticals, Merck & Co., Inc., MSD, Oncimmune, Pierre Fabre, Sairopa, Scorpion, Sellas, Skyline, TigaTX, and Trained Immunity TTC; payment or honoraria for lectures from IO Biotech, BMS, Merck & Co., Inc./MSD; participation on a Data Safety Monitoring Board for BioNTech, Boehringer Ingelheim, and Pfizer; and stock or stock options in IO Biotech, Sairopa, and SkylineDX.
(Copyright © 2024. Published by Elsevier Ltd.)