Background Options for patients with non-squamous non-small cell lung cancer (NSCLC) whose disease progresses after first-line chemotherapy are limited. This randomized, open-label, international phase 3 study evaluated efficacy and safety of nivolumab versus docetaxel in this patient population after failure of platinum doublet chemotherapy. Methods Patients were randomized to nivolumab 3 mg per kilogram every 2 weeks or docetaxel 75 mg per square meter every 3 weeks. The primary endpoint was overall survival. Results Nivolumab improved overall survival versus docetaxel. Median overall survival was 12.2 months (95% CI, 9.7 to 15.0) for nivolumab (n=292) and 9.4 months (95% CI, 8.1 to 10.7) for docetaxel (n=290) (hazard ratio, 0.73; 96% CI, 0.59 to 0.89; P=0.002). One-year overall survival rates were 51% (95% CI, 45 to 56) for nivolumab and 39% (95% CI, 33 to 45) for docetaxel. Updated efficacy results with additional follow up are available for overall survival only: 18-month overall survival rates were 39% (95% CI, 34 to 45) for nivolumab and 23% (95% CI, 19 to 28) for docetaxel. Response rates were 19% for nivolumab and 12% for docetaxel (P=0.02). Although progression-free survival did not favor nivolumab (2.3 months for nivolumab versus 4.2 months for docetaxel), 1-year progression-free survival was higher for nivolumab (19%) than docetaxel (8%). Nivolumab further improved efficacy across all endpoints at predefined ≥1%, ≥5%, and ≥10% programmed death-1 ligand 1 (PD-L1) tumor membrane expression levels. Grade 3–5 treatment-related adverse events were reported in 10% of nivolumab and 54% of docetaxel-treated patients. Conclusions Compared to docetaxel, nivolumab demonstrated superior overall survival, with PD-L1 expression conferring enhanced efficacy in patients with advanced non-squamous NSCLC after failure of platinum-based chemotherapy. The safety profile of nivolumab was favorable versus docetaxel.

Background Patients with advanced squamous-cell non–small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint–inhibitor antibody, as compared with docetaxel in this patient population. Methods We randomly assigned 272 patients to receive nivolumab, at a dose of 3 mg per kilogram of body weight every 2 weeks, or docetaxel, at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival. Results The median overall survival was 9.2 months (95% confidence interval [CI], 7.3 to 13.3) with nivolumab versus 6.0 months (95% CI, 5.1 to 7.3) with docetaxel. The risk of death was 41% lower with nivolumab than with docetaxel (hazard ratio, 0.59; 95% CI, 0.44 to 0.79; P<0.001). At 1 year, the overall survival rate was 42% (95% CI, 34 to 50) with nivolumab versus 24% (95% CI, 17 to 31) with docetaxel. The response rate was 20% with nivolumab versus 9% with docetaxel (P = 0.008). The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel (hazard ratio for death or disease progression, 0.62; 95% CI, 0.47 to 0.81; P<0.001). The expression of the PD-1 ligand (PD-L1) was neither prognostic nor predictive of benefit. Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the nivolumab group as compared with 55% of those in the docetaxel group. Conclusions Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level. (Funded by Bristol-Myers Squibb; CheckMate 017 ClinicalTrials.gov number, NCT01642004.)

Purpose Nivolumab, a programmed death-1 inhibitor, prolonged overall survival compared with docetaxel in two independent phase III studies in previously treated patients with advanced squamous (CheckMate 017; ClinicalTrials.gov identifier: NCT01642004) or nonsquamous (CheckMate 057; ClinicalTrials.gov identifier: NCT01673867) non-small-cell lung cancer (NSCLC). We report updated results, including a pooled analysis of the two studies. Methods Patients with stage IIIB/IV squamous (N = 272) or nonsquamous (N = 582) NSCLC and disease progression during or after prior platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m every 3 weeks). Minimum follow-up for survival was 24.2 months. Results Two-year overall survival rates with nivolumab versus docetaxel were 23% (95% CI, 16% to 30%) versus 8% (95% CI, 4% to 13%) in squamous NSCLC and 29% (95% CI, 24% to 34%) versus 16% (95% CI, 12% to 20%) in nonsquamous NSCLC; relative reductions in the risk of death with nivolumab versus docetaxel remained similar to those reported in the primary analyses. Durable responses were observed with nivolumab; 10 (37%) of 27 confirmed responders with squamous NSCLC and 19 (34%) of 56 with nonsquamous NSCLC had ongoing responses after 2 years' minimum follow-up. No patient in either docetaxel group had an ongoing response. In the pooled analysis, the relative reduction in the risk of death with nivolumab versus docetaxel was 28% (hazard ratio, 0.72; 95% CI, 0.62 to 0.84), and rates of treatment-related adverse events were lower with nivolumab than with docetaxel (any grade, 68% v 88%; grade 3 to 4, 10% v 55%). Conclusion Nivolumab provides long-term clinical benefit and a favorable tolerability profile compared with docetaxel in previously treated patients with advanced NSCLC.