Randomized phase II clinical trial of cisplatin/carboplatin and etoposide (PE) alone or in combination with nivolumab as frontline therapy for extensive‐stage small cell lung cancer (ES‐SCLC): ECOG‐ACRIN EA5161

Abstract Purpose Nivolumab showed durable responses in patients with small cell lung cancer (SCLC). A randomized phase II study investigating nivolumab plus cisplatin/carboplatin and etoposide (PE) versus PE for patients with untreated extensive‐stage (ES) SCLC was conducted. Methods Patients with untreated ES‐SCLC, Eastern Cooperative Oncology Group performance status 0‐1, were randomized 1:1 to nivolumab 360 mg intravenously (IV) plus cisplatin 75 mg/m 2 or carboplatin area under the curve 5 on day 1 and etoposide 100 mg/m 2 (PE) on days 1–3 every 21 days for four cycles followed by nivolumab 240 mg intravenously (arm A) every 2 weeks on a 6‐week cycle for up to 2 years or PE alone (Arm B) for 4 cycles followed by observation. The primary endpoint was progression‐free survival (PFS). The primary comparison of PFS used a logrank test stratified on the randomization stratification factors with a one‐sided type I error rate of 10%. Secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Results Overall, 160 patients were enrolled; 144 patients were treated and constituted the primary analysis. The median PFS was 5.5 months (95% confidence interval [CI], 4.3–5.9 months) on arm A, and 4.9 months (95% CI, 4.5–5.7 months) on arm B (hazard ratio, 0.78; p = .083). The estimated median OS was 11.2 months (95% CI, 8.8–14.2 months) on arm A and 8.1 months (95% CI, 7.2–9.6 months) on arm B (hazard ratio, 0.71; p = .059). Conclusion The combination of PE and nivolumab improves both PFS and OS for patients with ES‐SCLC. No new safety signals were observed.