• Scott J Antonia, Hossein Borghaei, Suresh S Ramalingam, Leora Horn, Javier De Castro Carpeño, Adam Pluzanski, Marco A Burgio, Marina Garassino, ChowLaura Q MLQMDivision of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA., Scott Gettinger, Lucio Crinò, David Planchard, Charles Butts, Alexander Drilon, Joanna Wojcik-Tomaszewska, Gregory A Otterson, Shruti Agrawal, Ang Li, John R Penrod, and Julie Brahmer.
• H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. Electronic address: scott.antonia@duke.edu.
• Lancet Oncol. 2019 Oct 1; 20 (10): 139514081395-1408.

BackgroundPhase 3 clinical data has shown higher proportions of patients with objective response, longer response duration, and longer overall survival with nivolumab versus docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC). We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival.MethodsWe pooled data from four clinical studies of nivolumab in patients with previously treated NSCLC (CheckMate 017, 057, 063, and 003) to evaluate survival outcomes. Trials of nivolumab in the second-line or later setting with at least 4 years follow-up were included. Comparisons of nivolumab versus docetaxel included all randomised patients from the phase 3 CheckMate 017 and 057 studies. We did landmark analyses by response status at 6 months to determine post-landmark survival outcomes. We excluded patients who did not have a radiographic tumour assessment at 6 months. Safety analyses included all patients who received at least one dose of nivolumab.FindingsAcross all four studies, 4-year overall survival with nivolumab was 14% (95% CI 11-17) for all patients (n=664), 19% (15-24) for those with at least 1% PD-L1 expression, and 11% (7-16) for those with less than 1% PD-L1 expression. In CheckMate 017 and 057, 4-year overall survival was 14% (95% CI 11-18) in patients treated with nivolumab, compared with 5% (3-7) in patients treated with docetaxel. Survival subsequent to response at 6 months on nivolumab or docetaxel was longer than after progressive disease at 6 months, with hazard ratios for overall survival of 0·18 (95% 0·12-0·27) for nivolumab and 0·43 (0·29-0·65) for docetaxel; for stable disease versus progressive disease, hazard ratios were 0·52 (0·37-0·71) for nivolumab and 0·80 (0·61-1·04) for docetaxel. Long-term data did not show any new safety signals.InterpretationPatients with advanced NSCLC treated with nivolumab achieved a greater duration of response compared with patients treated with docetaxel, which was associated with a long-term survival advantage.FundingBristol-Myers Squibb.Copyright © 2019 Elsevier Ltd. All rights reserved.

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