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.

• Authors: Jedd D Wolchok, Vanna Chiarion-Sileni, Rene Gonzalez, Jean-Jacques Grob, Piotr Rutkowski, Christopher D Lao, C Lance Cowey, Dirk Schadendorf, John Wagstaff, Reinhard Dummer, Pier Francesco Ferrucci, Michael Smylie, Marcus O Butler, Andrew Hill, Ivan Márquez-Rodas, John B A G Haanen, Massimo Guidoboni, Michele Maio, Patrick Schöffski, Matteo S Carlino, Céleste Lebbé, Grant McArthur, Paolo A Ascierto, Gregory A Daniels, Georgina V Long, Tuba Bas, Corey Ritchings, James Larkin, F Stephen Hodi
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 40 Issue 2 Pg. 127-137 (01 10 2022) ISSN: 1527-7755 [Electronic] United States
• PMID: 34818112 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Ipilimumab
• Nivolumab

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Disease Progression
• Humans
• Ipilimumab (adverse effects, therapeutic use)
• Melanoma (drug therapy, immunology, mortality, pathology)
• Neoplasm Staging
• Nivolumab (adverse effects, therapeutic use)
• Progression-Free Survival
• Skin Neoplasms (drug therapy, immunology, mortality, pathology)
• Time Factors