Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma

Abstract

PURPOSE In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety outcomes. PATIENTS AND METHODS Patients with previously untreated unresectable stage III or stage IV melanoma were randomly assigned 1:1:1 to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks (n = 314), nivolumab 3 mg/kg once every 2 weeks (n = 316), or ipilimumab 3 mg/kg once every 3 weeks (four doses; n = 315). Coprimary end points were progression-free survival and overall survival (OS) with nivolumab plus ipilimumab or nivolumab versus ipilimumab. Secondary end points included objective response rate, descriptive efficacy assessments of nivolumab plus ipilimumab versus nivolumab alone, and safety. Melanoma-specific survival (MSS; descriptive analysis), which excludes deaths unrelated to melanoma, was also evaluated. RESULTS Median OS (minimum follow-up, 6.5 years) was 72.1, 36.9, and 19.9 months in the combination, nivolumab, and ipilimumab groups, respectively. Median MSS was not reached, 58.7, and 21.9 months, respectively; 6.5-year OS rates were 57%, 43%, and 25% in patients with BRAF-mutant tumors and 46%, 42%, and 22% in those with BRAF–wild-type tumors, respectively. In patients who discontinued treatment, the median treatment-free interval was 27.6, 2.3, and 1.9 months, respectively. Since the 5-year analysis, no new safety signals were observed. CONCLUSION These 6.5-year CheckMate 067 results, which include the longest median OS in a phase III melanoma trial reported to date and the first report of MSS, showed durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab versus ipilimumab in patients with advanced melanoma and, in descriptive analyses, with the combination over nivolumab monotherapy.

Affiliated Institutions

• KU Leuven BE
• Université Paris Cité FR
• The Netherlands Cancer Institute NL
• Assistance Publique – Hôpitaux de Paris FR
• Royal Marsden Hospital GB
• Hospital General Universitario Gregorio Marañón ES
• UC San Diego Health System US
• Texas Oncology US
• Hôpital Saint-Louis FR
• Aix-Marseille Université FR
• Swansea University GB
• Istituti di Ricovero e Cura a Carattere Scientifico IT
• See-Spital CH
• Princess Margaret Cancer Centre CA
• Blacktown & Mount Druitt Hospital AU
• Melanoma Institute Australia AU
• Istituto Oncologico Veneto IT
• University of Siena IT
• Peter MacCallum Cancer Centre AU
• German Cancer Research Center DE
• Deutschen Konsortium für Translationale Krebsforschung
• Inserm FR
• University of Colorado Cancer Center US
• Oncode Institute NL
• Bristol-Myers Squibb (United States) US
• European Institute of Oncology IT
• The Maria Sklodowska-Curie National Research Institute of Oncology PL
• University of Colorado Denver US
• University of Michigan US
• Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IT
• Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" IT
• Dana-Farber Cancer Institute US
• Cornell University US
• The University of Sydney AU
• Memorial Sloan Kettering Cancer Center US
• Alberta Cancer Foundation CA

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