@article{f6b4cc5a4d5047b8926d0450f780a3f8,
title = "Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort",
abstract = "Introduction: Nivolumab monotherapy is approved in the United States for third-line or later metastatic small cell lung cancer based on pooled data from nonrandomized and randomized cohorts of the multicenter, open-label, phase 1/2 trial of nivolumab ± ipilimumab (CheckMate 032; NCT01928394). We report updated results, including long-term overall survival (OS), from the randomized cohort. Methods: Patients with small cell lung cancer and disease progression after one to two prior chemotherapy regimens were randomized 3:2 to nivolumab 3 mg/kg every 2 weeks or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four cycles followed by nivolumab 3 mg/kg every 2 weeks. Patients were stratified by number of prior chemotherapy regimens and treated until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by blinded independent central review. Results: Overall, 147 patients received nivolumab and 96 nivolumab plus ipilimumab. Minimum follow-up for ORR/progression-free survival/safety was 11.9 months (nivolumab) and 11.2 months (nivolumab plus ipilimumab). ORR increased with nivolumab plus ipilimumab (21.9% versus 11.6% with nivolumab; odds ratio: 2.12; 95% confidence interval: 1.06–4.26; p = 0.03). For long-term OS, minimum follow-up was 29.0 months (nivolumab) versus 28.4 months (nivolumab plus ipilimumab); median (95% confidence interval) OS was 5.7 (3.8–7.6) versus 4.7 months (3.1–8.3). Twenty-four–month OS rates were 17.9% (nivolumab) and 16.9% (nivolumab plus ipilimumab). Grade 3 to 4 treatment-related adverse event rates were 12.9% (nivolumab) versus 37.5% (nivolumab plus ipilimumab), and treatment-related deaths were n =1 versus n = 3, respectively. Conclusions: Whereas ORR (primary endpoint) was higher with nivolumab plus ipilimumab versus nivolumab, OS was similar between groups. In each group, OS remained encouraging with long-term follow-up. Toxicities were more common with combination therapy versus nivolumab monotherapy.",
keywords = "Immunotherapy, Ipilimumab, Programmed death-1 inhibitor, Small cell lung cancer: Nivolumab",
author = "Ready, {Neal E.} and Ott, {Patrick A.} and Hellmann, {Matthew D.} and Jon Zugazagoitia and Hann, {Christine L.} and {de Braud}, Filippo and Antonia, {Scott J.} and Ascierto, {Paolo A.} and Victor Moreno and Akin Atmaca and Stefania Salvagni and Matthew Taylor and Asim Amin and Camidge, {D. Ross} and Leora Horn and Emiliano Calvo and Ang Li and Lin, {Wen Hong} and Callahan, {Margaret K.} and Spigel, {David R.}",
note = "Funding Information: Disclosure: Dr. Ready has received fees to his institution from Bristol-Myers Squibb during the conduct of the study; has received grants from Merck; and has received personal fees from AbbVie, AstraZeneca, Bristol-Myers Squibb, Celgene, EMD Serono, G1 Therapeutics, Genetech, Merck, Novartis, and Tesaro. Dr. Ott has received grants from ARMO BioSciences, AstraZeneca, Bristol-Myers Squibb, Celldex, CytomX, Genentech, Neon Therapeutics, and Pfizer; and has received personal fees from Alexion, Amgen, Bristol-Myers Squibb, Celldex, CytomX, Genentech, Neon Therapeutics, Novartis, and Pfizer. Dr. Hellmann has received grants from Bristol-Myers Squibb; has received personal fees from AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, Janssen, Merck, Mirati, Nektar, Roche, Shattuck Labs, and Syndax; has received nonfinancial support from AstraZeneca and Bristol-Myers Squibb; and has a patent filed by MSK related to the use of tumor mutation burden to predict response to immunotherapy (PCT/US2015/062208), which has received licensing fees from PGDx. Dr. Zugazagoitia has received personal fees from Guardant Health outside the submitted work. Dr. Hann has received grants and research funds to his institution from AbbVie, Bristol-Myers Squibb, and Merrimack; and has received personal fees from Bristol-Myers Squibb, Genentech/Roche and Ascentage. Dr. de Braud has received personal fees from Amgen, Bristol-Myers Squibb, Daiichi Sankyo, EMD Serono, Ignyta, Incyte, Novartis, Octimet Oncology, Pfizer, Pharm Research Associated, Pierre Fabre, Roche, Servier, and Teofarma. Dr. Antonia has received personal fees from AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, CBMG, Memgen, Merck, and Novartis. Dr. Ascierto has received grants from Array, Bristol-Myers Squibb, and Roche/Genentech; and has received personal fees from 4SC, Array, AstraZeneca, Bristol-Myers Squibb, Genmab, Idera, Immunocore, Incyte, MedImmune, Merck Serono, MSD, NewLink Genetics, Novartis, Pierre Fabre, Roche/Genentech, Sandoz, Sanofi, Sun Pharma, Syndax, and Ultimovacs. Dr. Moreno has received personal fees from Bristol-Myers Squibb. Dr. Atmaca has received travel grants and personal fees from Bristol-Myers Squibb. Dr. Taylor has received grants from BioAtla; and has received personal fees from ArQule, Array BioPharma, Bayer, Blueprint Medicines, Bristol-Myers Squibb, Eisai Inc., Loxo Oncology, and Novartis. Dr. Amin has received personal fees from Array BioPharma, Bristol-Myers Squibb, Dynavax, Exelixis, Merck, Novartis, Pfizer, and Regeneron; and has received nonfinancial support from Bristol-Myers Squibb, Dynavax, and Merck. Dr. Camidge has received personal fees from Bristol-Myers Squibb. Dr. Horn has received research support paid to the institution by Bristol-Myers Squibb; has received personal fees from Abbvie, AstraZeneca, Bristol-Myers Squibb, Genetech-Roche, EMD Serono, Incyte, Merck, and Xcovery; and has received grants from Boehringer Ingelheim, Bristol-Myers Squibb, and Xcovery. Dr. Calvo has received personal fees from Abbvie, Alkerme, Amcure, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Cerulean Pharma, EUSA, GLG, Gehrmann Consulting, Gilead, Guidepoint, Janssen-Cilag, Medscape, Merck, Nanobiotix, Novartis, OncoDNA, Pfizer, Pierre Fabre, PsiOxus Therapeutics, Roche, Seattle Genetics, and Servier; holds leadership roles for INTHEOS, START Madrid, and HM Hospitals Group; stocks/ownership for International Cancer Consultants, Oncoart Associated, and START Madrid; has received research funding from AstraZeneca, Beigene, and Novartis; and has received fees to his institution from Abbvie, ACEO, Amcure, AMGEN, Astellas, AstraZeneca, BeiGene, Boehringen Ingelheim, Boston Therapeutics, Bristol-Myers Squibb, CytomX, Daiichi, DebioPharm, Dynavax, Genentech/Roche, GSK, H3, Incyte, Innovio, Janssen, Kura, Lilly, Loxo, Macrogenics, Menarini, Merck, Mersana, Merus, Millenium, MSD Nanobiotix, Nektar, Novartis, ORCA, Pfizer, PharmaMar, Principia, PsiOxus, PUMA, Regeneron, Rigontec, Sanofi, Seattle Genetics, Spectrum, Synthon, Taiho, Takeda, Tesaro, and Transgene. Dr. Callahan has received grants from Bristol-Myers Squibb; has received personal fees from AstraZeneca/MedImmune, Incyte, Merck, and Moderna; and a family member is employed at Bristol-Myers Squibb. Dr. Spigel has received grants to his institution from Bristol-Myers Squibb, AbbVie, Acerta Pharma, Aeglea Biotherapeutics, Amgen, ARMO Biosciences (Lilly), Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celldex, Clovis Oncology, Daiichi Sankyo, EMD Serono, Foundation Medicine, G1 Therapeutics, Genentech/Roche, GlaxoSmithKline, GRAIL, Ipsen, Lilly, Millennium, Nektar, Neon Therapeutics, Novartis, Oncogenex, Pfizer, Takeda, Tesaro, Transgene, and University of Texas-Southwestern; and has received fees for his institution from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, Evelo, Foundation Medicine, Genentech/Roche, GlaxoSmithKline, Illumina, Lilly, Merck, Moderna Therapeutics, Nektar, Novartis, Pfizer, PharmaMar, Precision Oncology, Takeda, and TRM Oncology. The remaining authors declare no conflict of interest.This study was supported by Bristol-Myers Squibb and ONO Pharmaceutical Company Ltd. The authors thank the patients and their families, as well as the participating trial teams, for making this trial possible; Candice Mayne for her contribution as protocol manager of this study; and Stephanie Meadows Shropshire for contributions to the statistical analysis plan. All authors have contributed to and approved this article; medical writing and editorial assistance was provided by Sharon Gladwin of Caudex, with funding from Bristol-Myers Squibb. Funding Information: This study was supported by Bristol-Myers Squibb and ONO Pharmaceutical Company Ltd. The authors thank the patients and their families, as well as the participating trial teams, for making this trial possible; Candice Mayne for her contribution as protocol manager of this study; and Stephanie Meadows Shropshire for contributions to the statistical analysis plan. All authors have contributed to and approved this article; medical writing and editorial assistance was provided by Sharon Gladwin of Caudex, with funding from Bristol-Myers Squibb . Publisher Copyright: {\textcopyright} 2019 International Association for the Study of Lung Cancer",
year = "2020",
month = mar,
doi = "10.1016/j.jtho.2019.10.004",
language = "English (US)",
volume = "15",
pages = "426--435",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "3",
}