Efficacy and Safety of Rechallenge with BRAF/MEK Inhibitors in Advanced Melanoma Patients: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Approximately 50% of patients with melanoma harbor a BRAF mutation and are eligible for targeted therapy with BRAF/MEK inhibitors (BRAFi/MEKi). Despite a response rate of nearly 70%, more than half of the patients will experience disease progression within a year due to tumor resistance. Rechallenging patients with BRAFi/MEKi has emerged as an alternative for improving response and survival outcomes. This systematic review and meta-analysis aims to investigate the efficacy and safety of this strategy in patients with advanced melanoma. ABSTRACT: This systematic review and meta-analysis aims to evaluate the efficacy and safety of rechallenging advanced melanoma patients with BRAFi/MEKi. Seven studies, accounting for 400 patients, were included. Most patients received immunotherapy before the rechallenge, and 79% underwent rechallenge with the combination of BRAFi/MEKi. We found a median progression-free survival of 5 months and overall survival of 9.8 months. The one-year survival rate was 42.63%. Regarding response, ORR was 34% and DCR 65%. There were no new or unexpected safety concerns. Rechallenge with BRAFi/MEKi can improve outcomes in advanced melanoma patients with refractory disease. These findings have significant implications for clinical practice, particularly in the setting of progressive disease in later lines and limited treatment options.