Nivolumab versus Docetaxel in a Predominantly Chinese Patient Population with Previously Treated Advanced Non-Small-Cell Lung Cancer: CheckMate 078 Randomised Phase 3 Clinical Trial

Abstract

BACKGROUND: Data on immuno-oncology agents in Chinese patients are limited despite a need for new therapies. We evaluated the efficacy and safety of nivolumab in a predominantly Chinese patient population with previously treated non-small-cell lung cancer (NSCLC). METHODS: CheckMate 078 was a randomised, open-label, phase 3 clinical trial enrolling patients from China, Russia, and Singapore with NSCLC whose disease progressed during/after platinum-based doublet chemotherapy. Patients (N=504) were included regardless of tumour histology and programmed death ligand 1 (PD-L1) expression; those with EGFR/ALK alterations were excluded. Patients were randomised 2:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks), stratified by performance status, histology, and tumour PD-L1 expression. The primary endpoint was overall survival (OS); secondary endpoints included objective response rate (ORR) and progression-free survival. FINDINGS: OS was significantly improved with nivolumab (n=338) versus docetaxel (n=166); median OS (95% CI), 12·0 (10·4-14·0) versus 9·6 (7·6- 11·2) months, respectively; hazard ratio (97·7% CI), 0·68 (0·52-0·90); p=0·0006. ORR was 17% with nivolumab versus 4% with docetaxel; median duration of response was not reached versus 5·3 months. Minimum follow-up was 8·8 months. The frequency of grade ≥3 treatment-related adverse events was 10% with nivolumab and 48% with docetaxel. INTERPRETATION: This is the first phase 3 study in a predominantly Chinese population reporting results with a PD-1 inhibitor. In this population with previously treated advanced NSCLC, nivolumab improved OS versus docetaxel. Results were consistent with global CheckMate 017 and 057 studies. CLINICAL TRIAL NUMBER: CheckMate 078 is registered on ClinicalTrials.gov, number NCT02613507. FUNDING STATEMENT: The study was funded by Bristol-Myers Squibb. Bristol-Myers Squibb was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. DECLARATION OF INTERESTS: Y-LW has received grants from Roche; has received personal fees from AstraZeneca, Eli Lilly, Pfizer, Roche, and Sanofi; and has received non-financial support from AstraZeneca. JW has received non-financial support from AstraZeneca. TM has received grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Eisai, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, SFJ Pharmaceuticals, Taiho, Takeda, and XCovery and has received personal fees from ACEA Biosciences, AstraZeneca, Boehringer Ingelheim, BristolMyers Squibb, Celgene, ChiMed, Clovis Oncology, Eli Lilly, Fishawack Facilitate Ltd, Ignyta Inc, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, OncoGenex, Pfizer, Roche/Genentech, SFJ Pharmaceuticals, Taiho, Takeda, and Vertex. CB and J Cai are employees of Bristol-Myers Squibb. All other authors report no competing interests. ETHICS APPROVAL STATEMENT: The study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation guidelines on good clinical practice. The study protocol was approved by an institutional review board or independent ethics committee at each site. An independent data monitoring committee monitored the activity and safety of nivolumab versus docetaxel throughout the study