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

Taofeek K. Owonikoko, Keunchil Park, Ramaswamy Govindan, Neal Ready, Martin Reck, Solange Peters, Shaker R. Dakhil, Alejandro Navarro, Jerónimo Rodríguez-Cid, Michael Schenker, Jong Seok Lee, Vanesa Gutierrez, Ivor Percent, Daniel Morgensztern, Carlos H. Barrios, Laurent Greillier, Sofia Baka, Miten Patel, Wen Hong Lin, Giovanni SelvaggiChristine Baudelet, Jonathan Baden, Dimple Pandya, Parul Doshi, Hye Ryun Kim

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145 Scopus citations


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 5 .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.

Original languageEnglish
Pages (from-to)1349-1359
Number of pages11
JournalJournal of Clinical Oncology
Issue number12
StatePublished - Apr 20 2021


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