The efficacy and safety of first-line metastatic melanoma treatment with ipilimumab + nivolumab vs. nivolumab in a real-world setting.

Abstract

The Checkmate 067 randomized controlled trial, published in 2015, demonstrated improved progression-free survival (PFS) and numerically, although not statistically, superior overall survival (OS) for ipilimumab + nivolumab (I + N). The objective of this study was to compare the efficacy and safety of N with I + N as first-line treatment for metastatic melanoma in a real-world setting. Patients were prospectively included in the French MelBase cohort from 2013 to 2022. Eligible patients were those in first-line treatment for stage IIIc or IV melanoma, undergoing immunotherapy with N or I + N. The primary endpoint was OS at 36 months. The secondary endpoints included PFS at 36 months, best radiological response, and safety analyses. We conducted a propensity score using the inverse probability of treatment weighting (IPTW) method to overcome the various confounding factors and also a subgroup analysis (brain metastasis, lactate dehydrogenase levels and BRAF mutation status). Patients were treated with N (n = 406) or I + N (n = 416). OS at 36 months was higher in the I + N group at 57.1% [95% confidence interval (CI) 50.7-64.2] than in the N group [46.6% (95% CI 41.6-52.1)]; hazard ratio (HR) 1.4 (95% CI 1.1-1.8). PFS at 36 months was significantly improved in the I + N group (42.3%) compared with the N group (21.9%), with a HR of 1.6 (95% CI 1.4-1.9). The objective response rate (ORR) was similar for the two groups (44%). The overall incidence of side-effects was comparable (82% vs. 84%), and severe toxicity (grade ≥ 3) was more frequent, although not significantly so, in the I + N arm vs. the N arm (41% vs. 29%). Our results are consistent with those from the Checkmate 067 study, except for the ORR and the incidence of toxicities, which proved to be lower in our analysis.