New emerging treatment options for metastatic melanoma: a systematic review and meta-analysis of skin cancer therapies

Abstract

Skin cancer, notably melanoma, poses a significant global health burden, with rising incidence and mortality rates. While therapeutic advancements have improved outcomes, metastatic melanoma remains challenging to treat. This study aims to systematically review systemic treatment options for advanced melanoma, focusing on efficacy and safety in the first-line setting. Through a comprehensive search and meta-analysis of randomized controlled trials conducted from 2013 to 2023, 11 studies encompassing 2816 participants were analyzed. Treatment options included BRAF inhibitors (vemurafenib, dabrafenib), MEK inhibitors (trametinib, cobimetinib), and immune checkpoint inhibitors (ipilimumab). Combined therapy with vemurafenib, cobimetinib, and ipilimumab demonstrated superior overall survival (OS) and progression-free survival (PFS) compared to monotherapy, with a significant odds ratio (OR) of 6.95 (95% CI: 4.25–9.64, p < 0.00001) for OS and 2.49 (95% CI: 1.42–3.56, p < 0.00001) for PFS. Additionally, dabrafenib and trametinib combination therapy showed improved outcomes with favorable tolerability, including a significant reduction in adverse event (AE) risk, with an OR of 2.20 (95% CI: 1.72–2.81). Furthermore, our analysis highlighted vemurafenib-associated dermatological toxicities, emphasizing the need for effective management strategies. The study underscores the evolving treatment landscape in melanoma management, with a potential shift towards immune checkpoint inhibitors in the adjuvant setting, particularly for BRAF-mutated disease. However, limitations in meta-analysis methodologies and the need for long-term investigations into treatment implications on survival and quality of life underscore the importance of continued research.