Second-Line Nivolumab in Relapsed Small-Cell Lung Cancer: CheckMate 331.

BACKGROUND Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase 1/2 data show activity of nivolumab in previously treated SCLC. PATIENTS AND METHODS CheckMate 331 is a randomized, open-label, phase 3 trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line platinum-based chemotherapy were randomized 1:1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS). RESULTS Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy (median OS, 7.5 vs 8.4 months; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.72-1.04; P = 0.11). A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab vs chemotherapy) was similar in patients with programmed death ligand 1 combined positive score ≥ 1% versus < 1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%. CONCLUSION Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.