@article{76ace62f54094af4aaef7594d0745c91,
title = "Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases",
abstract = "Background: Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥ 3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC. Patients and methods: Patients were randomized 1: 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses. Results: After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50-0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61-0.81). Rates of treatment-related hepatic adverse events (primarily grade 1-2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%). Conclusions: After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated.",
keywords = "Liver metastases, NSCLC, Nivolumab",
author = "Vokes, {Everett E.} and N. Ready and E. Felip and L. Horn and Burgio, {M. A.} and Antonia, {S. J.} and Frontera, {O. Ar{\'e}n} and S. Gettinger and E. Holgado and D. Spigel and D. Waterhouse and M. Domine and M. Garassino and Chow, {L. Q.M.} and G. Blumenschein and F. Barlesi and B. Coudert and J. Gainor and O. Arrieta and J. Brahmer and C. Butts and M. Steins and Geese, {W. J.} and A. Li and D. Healey and L. Crin{\`o}",
note = "Funding Information: The authors thank the patients and their families for making these studies possible, as well as the clinical study teams (complete lists of CheckMate 017 and CheckMate 057 investigators are shown in supplementary Tables S5 and S6, available at Annals of Oncology online) who participated in the trials. They also thank Dako for collaborative development of the automated PD-L1 immunohistochemistry assay, Bristol-Myers Squibb (Princeton, USA), and ONO Pharmaceutical Company Ltd. (Osaka, Japan). All authors contributed to and approved the manuscript. Medical writing and editorial assistance was provided by Kerry K. Brinkman, PhD, of Evidence Scientific Solutions, and was funded by Bristol-Myers Squibb. Funding Information: Bristol-Myers Squibb (no grant number applies). Funding Information: EEV received personal fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Leidos, Merck, Regeneron, Serono, Takeda, and VentiRx. NR received personal fees from Abbvie, Celgene, Bristol-Myers Squibb, and Merck. EF received personal fees or participated in a speaker{\textquoteright}s bureau for AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardanthealth, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda. LH received personal fees from Abbvie, AstraZeneca, Bristol-Myers Squibb, Lilly, Merck, and Roche-Genentech; and other from Boehringer-Ingelheim and Xcovery. SJA received other from AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, CBMG, Genentech, Memgen, Merck, and Novartis. SG received grants from ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Incyte, and Pfizer; personal fees from ARIAD, Bristol-Myers Squibb, and Janssen. DW received personal fees from Abbvie, Amgen, Celgene, Bristol-Myers Squibb, and Roche-Genentech. MG received other from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, and Roche. LQMC received grants and other from AstraZeneca, Bristol-Myers Squibb, Genentech, Novartis, Pfizer, and Seattle Genetics; grants from Incyte, and VentiRx; and other from Amgen, ImClone, Merck, and Sanofi-Genzyme. GB received grants, personal fees and other from Bayer, Bristol-Myers Squibb, Celgene, and Merck; personal fees and other from Abbvie, ARIAD, and Clovis; grants and personal fees from AstraZeneca, Genentech, Novartis, and Xcovery; and grants from Adaptimmune, GlaxoSmithKline, Immatics, and Macrogenetics. FB received personal fees from AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd, Novartis, Merck, Merck Sharp & Dohme, Pierre Fabre, and Pfizer. BC received personal fees from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Genomic Health, and Lilly; and personal fees and nonfinancial support from Pfizer and Roche. JG received personal fees and other from Ariad, Clovis, Bristol-Myers Squibb, Genentech/Roche, Incyte, Loxo, Merck, Novartis, Pfizer, and Takeda. OA received personal fees from Bristol-Myers Squibb. JB received grants and nonfinancial support from Bristol-Myers Squibb and Merck; personal fees from Celgene, and Lilly; and grants from MedImmune/AstraZeneca. CB received other from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, and Pfizer. MS received personal fees from Bristol-Myers Squibb. WJG received personal fees from and holds stock in Bristol-Myers Squibb. AL received personal fees from Bristol-Myers Squibb. DH received personal fees from Bristol-Myers Squibb and holds stock in Pfizer. All remaining authors have declared no conflicts of interest.",
year = "2018",
month = apr,
day = "1",
doi = "10.1093/annonc/mdy041",
language = "English (US)",
volume = "29",
pages = "959--965",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "4",
}