College of Pharmacy, Al Ain University, Abu Dhabi, United Arab Emirates.
Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110, Jordan.
Arch Dermatol Res. 2024 Nov 1;316(10):735. doi: 10.1007/s00403-024-03467-2.
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.
皮肤癌，尤其是黑色素瘤，对全球健康构成重大负担，其发病率和死亡率呈上升趋势。虽然治疗进展提高了疗效，但转移性黑色素瘤的治疗仍然具有挑战性。本研究旨在系统综述晚期黑色素瘤的全身治疗选择，重点关注一线治疗中的疗效和安全性。通过对 2013 年至 2023 年进行的随机对照试验进行全面搜索和荟萃分析，分析了包括 2816 名参与者的 11 项研究。治疗选择包括 BRAF 抑制剂（vemurafenib、dabrafenib）、MEK 抑制剂（trametinib、cobimetinib）和免疫检查点抑制剂（ipilimumab）。与单药治疗相比，vemurafenib、cobimetinib 和 ipilimumab 的联合治疗显示出更好的总生存期（OS）和无进展生存期（PFS），OS 的优势比（OR）为 6.95（95%CI：4.25-9.64，p<0.00001），PFS 的 OR 为 2.49（95%CI：1.42-3.56，p<0.00001）。此外，dabrafenib 和 trametinib 的联合治疗显示出更好的疗效和良好的耐受性，包括不良事件（AE）风险的显著降低，OR 为 2.20（95%CI：1.72-2.81）。此外，我们的分析还强调了 vemurafenib 相关的皮肤毒性，需要有效的管理策略。该研究强调了黑色素瘤管理中治疗方法的不断发展，特别是在 BRAF 突变疾病中，免疫检查点抑制剂在辅助治疗中的应用可能会发生转变。然而，荟萃分析方法的局限性以及对治疗对生存和生活质量影响的长期研究的需要，突显了持续研究的重要性。
