The Efficacy And Safety Of The Combination Of Anti-Braf Agent And Mek Inhibitor In Advanced Melanoma Patients With Braf V600 Mutation: A Meta-Analysis.

e20006 Background: The combination of anti-BRAF agent and MEK inhibitor has been shown to improve outcomes for advanced melanoma patients with BRAF V600E mutation. A meta-analysis was performed to evaluate the efficacy and safety of the combination of anti-BRAF agent and MEK inhibitor in these patients. Methods: Eligible trials were phase II or phase III randomized controlled trials (RCTs) comparing the combination therapy with anti-BRAF agent alone in advanced melanoma with BRAF V600E mutation reporting progression-free survival (PFS) , overall survival (OS), objective response rates(ORR) and adverse effects. Results: Four trials with five comparisons comprising 1784 patients were eligible for inclusion. BRAF inhibitors were vemurafenib and dabrafenib; MEK inhibition were trametinib and cobimetinib. The combination therapy improved PFS [hazard ratios (HR) 0.56; 95% confidence interval (CI) 0.47–0.68], OS (HR0.69; 95% CI 0.57–0.82], and ORR [relative risk (RR) 1.31; 95% CI 1.17–1.47]. There was no significant difference regarding overall grade 3 or higher adverse effects between them (RR 1.00; 95% CI 0.86-1.17). However, the risk of developing cutaneous squamous cell carcinoma and keratoacanthoma was significantly decreased about 80% in the combination arm (RR 0.19; 95% CI 0.10-0.36). Conclusions: Our meta-analysis suggests the benefit of combination therapy of anti-BRAF agent and MEK inhibitor for advanced melanoma patients with BRAF V600E mutation as first-line treatment, as well as decreased risk of developing cutaneous squamous cell carcinoma and keratoacanthoma. Trials in our meta-analysis differed in terms of anti-BRAF agents and MEK inhibitors, yet delivered comparable outcomes.