Résumé
Background 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).Objectives 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.Methods 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).Results 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%).Conclusions 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.
Over recent decades, we have seen an increase in the incidence of melanomas at all stages. New therapies, including immunotherapy, have improved the prognosis for metastatic melanoma (MM). Immunotherapy is now widely prescribed for treating metastatic forms. It is used as an adjuvant treatment (after the primary treatment) to prevent relapse. Recent research has shown the efficacy of immunotherapy, in particular, dual immunotherapy.Our study is of more than 800 patients with MM from a large French multicentre cohort. We compared nivolumab alone and ipilimumab with nivolumab (I + N) as a first-line therapy in real life for patients with MM. We saw a clear improvement in progression-free survival with dual immunotherapy (I + N). We also saw a small improvement in overall survival, compared with nivolumab alone. We saw an increase in severe toxicities for patients treated with I + N, but less than noted in the literature.This large real-life study supports the results of randomized controlled trials to use dual immunotherapy to treat MM.
The Checkmate 067 trial showed that ipilimumab + nivolumab (I + N) improved progression-free survival (PFS) and had a numerically superior overall survival (OS) compared with N alone. This study aimed to compare these treatments in a real-world setting, and found that I + N led to higher OS and PFS at 36 months, although with slightly more severe toxicities. The results largely align with Checkmate 067, except for a lower incidence of toxicities and a similar objective response rate in both groups.