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.)

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The IASLC Staging and Prognostic Factors Committee has collected a new database of 94,708 cases donated from 35 sources in 16 countries around the globe. This has now been analysed by our statistical partners at Cancer Research And Biostatistics and, in close collaboration with the members of the committee proposals have been developed for the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published late 2016. In this publication we describe the methods used to evaluate the resultant Stage groupings and the proposals put forward for the 8th edition.

BACKGROUND: Approved systemic treatments for malignant pleural mesothelioma (MPM) were limited to chemotherapy regimens that have moderate survival benefit with poor outcomes. Nivolumab plus ipilimumab showed clinical benefit in other tumour types, including first-line non-small cell lung cancer. We hypothesised that this regimen would improve overall survival in MPM. METHODS:This open-label phase 3 study was conducted at 103 hospitals across 21 countries. Adults with previously untreated, histologically confirmed unresectable MPM were randomised (1:1) to nivolumab (3 mg/kg intravenously Q2W) plus ipilimumab (1 mg/kg intravenously Q6W) for ≤2 years, or platinum plus pemetrexed chemotherapy (pemetrexed [500 mg/m 2 intravenously] plus cisplatin [75 mg/m 2 intravenously] or carboplatin [AUC 5 mg/mL/min intravenously]) Q3W for up to 6 cycles. The primary endpoint was overall survival (all randomised patients); safety was assessed in all treated patients. This study is registered with ClinicalTrials.gov, NCT02899299. FINDINGS:Between November 29, 2016 and April 18, 2018, 713 patients were enrolled; 303 were randomised to nivolumab plus ipilimumab and 302 to chemotherapy. At the prespecified interim analysis (median follow-up 29•7 months [IQR,[26][27][28][29][30][31][32]), nivolumab plus ipilimumab significantly prolonged overall survival versus chemotherapy. Median overall survival was 18•1 months (95% CI 16•8-21•4) versus 14•1 months (95% CI 12•4-16•2), with a hazard ratio of 0•74 (96•6% CI 0•60-0•91; p=0•0020); 2year overall survival rates were 41% (95% CI 35•1-46•5) and 27% (95% CI 21•9-32•4), respectively.Grade 3-4 treatment-related adverse events were reported in 91 (30%) of 300 patients treated with nivolumab plus ipilimumab and 91 (32%) of 284 treated with chemotherapy. There were three (1%) and one (<1%) treatment-related deaths, respectively. INTERPRETATION:Nivolumab plus ipilimumab provided statistically significant and clinically meaningful improvements in overall survival versus standard-of-care chemotherapy, supporting the use of this first-in-class approved (United States) regimen for previously untreated unresectable MPM.