Combination Ipilimumab/Nivolumab Better Than Single-Agent Anti–PD-1 Regardless of BRAF Status in Advanced Melanoma

The combination of ipilimumab (Yervoy) plus nivolumab (Opdivo) appears to be superior to a single-agent PD-1 inhibitor in patients with metastatic melanoma regardless of BRAF mutation status, according to the results of a single-center retrospective analysis of a cohort of more than 300 patients.

The findings run counter to those from the CheckMate-067 trial, which found improved progression-free survival (PFS) and overall survival (OS) with the combination compared with nivolumab alone in patients with BRAF-mutant metastatic melanoma, and no significant difference between the treatments in the BRAF wild-type cohort.

Results of the analysis were presented in poster format by researchers led by Vincent T. Ma, MD, Oncology/Hematology Fellow, University of Michigan, Ann Arbor, during the American Society of Clinical Oncology 2020 Virtual Scientific Program.

“In our analysis, unresectable or metastatic melanoma patients with BRAF wild-type status treated with combination ipilimumab/nivolumab had an increased likelihood of survival compared to patients treated with PD-1 inhibitor,” the investigators concluded.

They identified 323 patients with metastatic or unresectable melanoma diagnosed between 2012 and 2109 at the University of Michigan, 132 with BRAF V600 mutation and 191 with BRAF wild-type disease. A total of 138 patients received ipilimumab/nivolumab and 185 received a PD-1 inhibitor alone.

On univariate analysis, neither PFS (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.46-1.13) nor OS (HR, 0.78; 95% CI, 0.44-1.38) were significantly different between patients treated with ipilimumab/nivolumab versus a PD-1 inhibitor alone in the BRAF-mutant cohort. However, both PFS (HR, 0.55; 95% CI, 0.35-0.88) and OS (HR, 0.52; 95% CI, 0.28-0.95) were improved in the combination immunotherapy arm versus the monotherapy arm in patients with BRAF wild-type melanoma.

On multivariate analysis, PFS remained significantly superior with the ipilimumab/nivolumab combination versus PD-1 inhibitor monotherapy in the BRAF wild-type cohort (HR, 0.575; 95% CI, 0.35-0.95). The benefit to combination immunotherapy on OS in this subset, however, lost statistical significance (HR, 0.54; 95% CI, 0.28-1.03).

“Due to higher rates of toxicities with ipilimumab/nivolumab, further studies are warranted to identify which patient subgroups may benefit more from combination immunotherapy,” the investigators concluded.

Source: Ma VTL, Daignault S, Waninger J, et al. The impact of BRAF mutation status on clinical outcomes with single-agent PD-1 inhibitor versus combination ipilimumab/nivolumab. J Clin Oncol. 2020;38(15_suppl). Abstract 10024.

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