Efficacy and safety of nivolumab (nivo) monotherapy versus chemotherapy (chemo) in recurrent small cell lung cancer (SCLC): Results from CheckMate 331

Abstract

Background: Despite high initial response rates, most patients (pts) with SCLC relapse soon after first-line (1L) treatment (tx), with limited tx options and a poor prognosis. Nivo is approved in the US for tx of metastatic SCLC with progression after platinum-based chemo and !1 other line of tx. We report results from CheckMate 331 (NCT02481830), a global, open-label, phase 3 trial of nivo vs chemo in pts with relapsed SCLC after 1L platinum-based chemo. Methods: Pts (N ¼ 569) with limited-or extensive-disease SCLC and recurrence/pro-gression after 1L platinum-based chemo were randomized 1:1 to receive nivo (n ¼ 284) or chemo (n ¼ 285; topotecan or amrubicin where locally approved; see Table for all dosages), stratified by platinum sensitivity (90 days) and CNS metastases. Pts were treated until progression (or no longer deriving clinical benefit with nivo) or unacceptable toxicity. Primary endpoint was overall survival (OS) with nivo vs chemo. Approximately 482 events were expected, providing 90% power to detect a hazard ratio (HR) of 0.745 favoring nivo (2-sided alpha, 0.05). Results: Minimum follow-up was 15.8 months. Baseline characteristics were balanced between arms. No statistically significant improvement in OS was seen with nivo vs chemo (HR, 0.86 [95% CI, 0.72-1.04]); however OS curves showed delayed separation after month 12. HR for OS with nivo vs chemo in pts with platinum-resistant SCLC was 0.71 (95% CI, 0.54-0.94). Other efficacy outcomes are shown in the table. All-grade (grade 3-4) tx-related adverse events (AE) occurred in 55% (14%) of nivo-and 90% (73%) of chemo-treated pts. There were 2 tx-related deaths with nivo and 3 with chemo.