The Evaluation of Immune Checkpoint Inhibitors and BRAF/MEK Inhibitors in Different Therapy Lines for Metastatic Melanoma: A Retrospective Study

Background: Nivolumab plus ipilimumab (nivo/ipi) combination therapy is highly effective in treating advanced melanoma, but serious immune-related adverse events (irAEs) are prevalent. The overall response rate (ORR) of the BRAF inhibitor plus MEK inhibitor (BRAFi/MEKi) combination therapy for BRAFV600-mutant advanced melanoma surpasses that of immune checkpoint inhibitors (ICIs). However, the OS and PFS of BRAFi/MEKi combination therapy are inferior to those of ICIs. Methods: We retrospectively evaluated 22 melanoma patients treated with nivo/ipi therapy and 13 patients treated with encorafenib plus binimetinib (enco/bini) between November 2018 and July 2023. Results: The ORR of nivo/ipi for metastatic melanoma patients was significantly higher in the first-line cohort 60.0% (95% CI: 31.2–83.3%) than in the second-line or beyond cohort 8.3% (95% CI: 0–37.5%), whereas the ORR of enco/bini was comparable between the first-line cohort 75.0% (95% CI: 28.9–96.6%) and the second-line or beyond cohort 77.8% (95% CI: 44.3–94.7%). The median PFS of nivo/ipi significantly improved in the first-line cohort 7.7 months (95% CI: 2.0–11.9) compared to the second-line or beyond cohort 2.3 months (95% CI: 0.5–6.0) (p = 0.0109). In addition to efficacy, the incidence of grade 3 or greater AEs was comparable in the first-line and second-line or beyond cohorts. Conclusions: Although our present data are based on a small number of cases, they suggest that nivo/ipi should be administered as the first-line therapy for the treatment of BRAFV600-mutant metastatic melanoma, rather than enco/bini, aligning with findings from previous clinical trials.