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.)

BACKGROUND Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti–programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition. METHODS In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life. RESULTS The median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to 6.0) in the group that received standard therapy. Overall survival was significantly longer with nivolumab than with standard therapy (hazard ratio for death, 0.70; 97.73% CI, 0.51 to 0.96; P = 0.01), and the estimates of the 1-year survival rate were approximately 19 percentage points higher with nivolumab than with standard therapy (36.0% vs. 16.6%). The median progression-free survival was 2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to 3.1) with standard therapy (hazard ratio for disease progression or death, 0.89; 95% CI, 0.70 to 1.13; P = 0.32). The rate of progression-free survival at 6 months was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was 13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the nivolumab group versus 35.1% of those in the standard-therapy group. Physical, role, and social functioning was stable in the nivolumab group, whereas it was meaningfully worse in the standard-therapy group. CONCLUSIONS Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy. (Funded by Bristol-Myers Squibb; CheckMate 141 ClinicalTrials.gov number, NCT02105636.)

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