Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: CheckMate 451.

Journal Article (Clinical Trial, Phase III;Journal Article)

PURPOSE: In extensive-disease small-cell lung cancer (ED-SCLC), response rates to first-line platinum-based chemotherapy are robust, but responses lack durability. CheckMate 451, a double-blind phase III trial, evaluated nivolumab plus ipilimumab and nivolumab monotherapy as maintenance therapy following first-line chemotherapy for ED-SCLC. METHODS: Patients with ED-SCLC, Eastern Cooperative Oncology Group performance status 0-1, and no progression after ≤ 4 cycles of first-line chemotherapy were randomly assigned (1:1:1) to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 12 weeks followed by nivolumab 240 mg once every 2 weeks, nivolumab 240 mg once every 2 weeks, or placebo for ≤ 2 years or until progression or unacceptable toxicity. Primary end point was overall survival (OS) with nivolumab plus ipilimumab versus placebo. Secondary end points were hierarchically tested. RESULTS: Overall, 834 patients were randomly assigned. The minimum follow-up was 8.9 months. OS was not significantly prolonged with nivolumab plus ipilimumab versus placebo (hazard ratio [HR], 0.92; 95% CI, 0.75 to 1.12; P = .37; median, 9.2 v 9.6 months). The HR for OS with nivolumab versus placebo was 0.84 (95% CI, 0.69 to 1.02); the median OS for nivolumab was 10.4 months. Progression-free survival HRs versus placebo were 0.72 for nivolumab plus ipilimumab (95% CI, 0.60 to 0.87) and 0.67 for nivolumab (95% CI, 0.56 to 0.81). A trend toward OS benefit with nivolumab plus ipilimumab was observed in patients with tumor mutational burden ≥ 13 mutations per megabase. Rates of grade 3-4 treatment-related adverse events were nivolumab plus ipilimumab (52.2%), nivolumab (11.5%), and placebo (8.4%). CONCLUSION: Maintenance therapy with nivolumab plus ipilimumab did not prolong OS for patients with ED-SCLC who did not progress on first-line chemotherapy. There were no new safety signals.

Full Text

Duke Authors

Cited Authors

  • Owonikoko, TK; Park, K; Govindan, R; Ready, N; Reck, M; Peters, S; Dakhil, SR; Navarro, A; Rodríguez-Cid, J; Schenker, M; Lee, J-S; Gutierrez, V; Percent, I; Morgensztern, D; Barrios, CH; Greillier, L; Baka, S; Patel, M; Lin, WH; Selvaggi, G; Baudelet, C; Baden, J; Pandya, D; Doshi, P; Kim, HR

Published Date

  • April 20, 2021

Published In

Volume / Issue

  • 39 / 12

Start / End Page

  • 1349 - 1359

PubMed ID

  • 33683919

Pubmed Central ID

  • PMC8078251

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Digital Object Identifier (DOI)

  • 10.1200/JCO.20.02212


  • eng

Conference Location

  • United States