Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Via Mariano Semmola snc, Naples, Italy.
Department of Medicine (DAME), University Hospital of Udine, Udine, Italy.
Curr Oncol Rep. 2019 Jul 29;21(9):76. doi: 10.1007/s11912-019-0827-x.
The treatment of advanced melanoma has changed dramatically in recent years with several new drugs having been approved for the treatment of melanoma since 2011. This review aims to evaluate the role of BRAF-targeted therapy for advanced melanoma in the immunotherapy era.
Currently, in patients with BRAF wild-type advanced melanoma, anti-PD-1 (nivolumab or pembrolizumab) is the main treatment. The combination of nivolumab and ipilimumab (anti-CTLA-4) is also an important option for these patients, resulting in a better outcome, but with less favorable toxicity profile. In patients with BRAF mutations, three regimens of BRAF plus MEK inhibitors are now approved (vemurafenib plus cobimetinib, dabrafenib plus trametinib, and encorafenib plus binimetinib), which achieve rapid antitumor responses and a significant survival benefit. In these patients, as well as in BRAF wild-type patients, immunotherapy can be also effective and is regularly used. Immunotherapy and targeted therapy have become the new standards of care, substantially improving survival rates. However, many questions still remain unanswered, such as what is the best first- and second-line treatment and the best treatment sequence. New combinations of drugs, targeted therapy combined with immunotherapy, and sequencing approaches are now underway in many ongoing clinical trials.
自 2011 年以来，已有几种新药被批准用于治疗黑色素瘤，因此近年来晚期黑色素瘤的治疗发生了巨大变化。本篇综述旨在评估在免疫治疗时代 BRAF 靶向治疗在晚期黑色素瘤中的作用。
目前，在 BRAF 野生型晚期黑色素瘤患者中，抗 PD-1（nivolumab 或 pembrolizumab）是主要治疗方法。nivolumab 和 ipilimumab（抗 CTLA-4）联合也是这些患者的重要选择，这导致了更好的结果，但毒性特征不太有利。在 BRAF 突变的患者中，现在有三种 BRAF 加 MEK 抑制剂方案获得批准（vemurafenib 加 cobimetinib、dabrafenib 加 trametinib 和 encorafenib 加 binimetinib），这些方案可实现快速抗肿瘤反应和显著的生存获益。在这些患者以及 BRAF 野生型患者中，免疫疗法也可能有效，并且经常使用。免疫疗法和靶向疗法已成为新的护理标准，大大提高了生存率。然而，仍有许多问题尚未得到解答，例如什么是最佳的一线和二线治疗以及最佳的治疗顺序。目前正在许多正在进行的临床试验中开展新的药物组合、靶向疗法联合免疫疗法以及治疗顺序方法。
