LBA1_PR - Nivolumab (nivo) plus ipilimumab (ipi), nivo, or placebo (pbo) as maintenance therapy in patients (pts) with extensive disease small cell lung cancer (ED-SCLC) after first-line (1L) platinum-based chemotherapy (chemo): Results from the double-blind, randomized phase III CheckMate 451 study

Abstract

Background: In pts with ED-SCLC, response rates to 1L platinum-based chemo are high but lack durability. Treatments (txs) that prolong response duration and improve survival are needed. CheckMate 451 (NCT02538666) is a global, double-blind, phase 3 study of nivo+ipi or nivo vs pbo as maintenance therapy in pts with ED-SCLC who did not progress on 1L platinum-based chemo.

Methods: Pts (N = 834) with ED-SCLC, ECOG performance status (PS) ≤ 1 and response or stable disease after 4 cycles of 1L platinum-based chemo were randomized 1:1:1 (3–9 weeks from last dose of 1L chemo or 3–11 weeks for pts who received prophylactic cranial irradiation [PCI]) to nivo 1 mg/kg + ipi 3 mg/kg Q3W intravenously (IV; 4 doses followed by nivo 240 mg Q2W IV; n = 279), nivo 240 mg Q2W IV (n = 280), or pbo (n = 275), stratified by PS, sex and prior PCI. Pts were treated up to 2 years or until progression or unacceptable toxicity. Primary endpoint was overall survival (OS) for nivo+ipi vs pbo. Secondary endpoints included OS for nivo vs pbo and progression-free survival (PFS) per blinded independent central review for nivo+ipi vs pbo and nivo vs pbo.

Results: Minimum study follow-up was 9 months. Baseline characteristics were balanced between arms. OS was not significantly prolonged with nivo+ipi vs pbo (HR, 0.92; 95% CI 0.75–1.12; P = 0.3693). OS was also not prolonged for nivo vs pbo (HR, 0.84; 95% CI 0.69–1.02), although not formally tested due to statistical hierarchy. PFS HRs vs pbo were: nivo+ipi, 0.72 (0.60–0.87); nivo, 0.67 (0.56–0.81). Rates of all-grade (grade 3–4) tx-related adverse events were: nivo+ipi, 86% (52%); nivo, 61% (12%); pbo, 50% (8%). Rates of discontinuation due to tx toxicity were: nivo+ipi, 31%; nivo, 9%; pbo, <1%. Tx-related deaths were: nivo+ipi, 7 (2.5%); nivo, 1 (<1%); pbo, 1 (<1%).

Conclusions: In CheckMate 451, maintenance therapy with nivo+ipi (primary endpoint) or nivo did not prolong OS vs pbo for ED-SCLC patients who did not progress on 1L chemo. Safety profiles of nivo+ipi and nivo were consistent with previous reports at this dose/schedule in SCLC.

Clinical trial identification: NCT02538666; Release date: 2 September 2015.