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

<b>Background</b>: 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 <i>BRAF^V600</i>-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. <b>Methods</b>: 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. <b>Results</b>: 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)] (<i>p</i> = 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. <b>Conclusions</b>: 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 <i>BRAF^V600</i>-mutant metastatic melanoma, rather than enco/bini, aligning with findings from previous clinical trials.