Amaral Teresa, Nouri Noura, Garbe Claus
a Center for Dermatooncology, Department of Dermatology , University Hospital Tübingen , Tübingen , Germany.
b Military Health Care Department , Portuguese Air Force Health Direction , Lisbon , Portugal.
Expert Rev Anticancer Ther. 2016 Jul;16(7):705-15. doi: 10.1080/14737140.2016.1192469. Epub 2016 Jun 10.
In the recent years, melanoma patients' outcome and survival improved, mainly because of systemic treatment improvement with targeted therapy and checkpoint blockade. Targeted therapy with BRAF and MEK inhibitors was approved to treat patients with unresectable or metastatic melanoma, harboring BRAF V600 mutations. This paper addresses the safety and efficacy of cobimetinib, when used in combination with vemurafenib, in the previous mentioned setting.
This article presents an overview on the rationale for clinical development of cobimetinib, as well as the mechanism of action, the efficacy and safety, and the most important trials that led to the approval of the combination therapy with vemurafenib. We searched the PubMed for published papers related to safety and efficacy of cobimetinib, and resistance mechanisms to BRAF inhibition. The abstract databases of the American Society of Clinical Oncology and European Society for Medical Oncology were also searched for updates on the mentioned clinical trials. Expert commentary: Patients treated with targeted therapy experience a rapid tumor response. However, virtually all patients will develop resistance to treatment. Therapeutic combinations to overcome resistance mechanisms are currently addressed. In the future, targeted therapy strategy will include three or more drugs, probably from different therapeutic classes.
近年来，黑色素瘤患者的预后和生存率有所改善，这主要归功于靶向治疗和免疫检查点阻断等全身治疗方法的改进。BRAF和MEK抑制剂的靶向治疗已被批准用于治疗携带BRAF V600突变的不可切除或转移性黑色素瘤患者。本文探讨了在上述情况下，考比替尼与维莫非尼联合使用时的安全性和有效性。
本文概述了考比替尼临床开发的基本原理、作用机制、疗效和安全性，以及导致维莫非尼联合疗法获批的最重要试验。我们在PubMed上搜索了与考比替尼安全性和有效性以及BRAF抑制耐药机制相关的已发表论文。还搜索了美国临床肿瘤学会和欧洲医学肿瘤学会的摘要数据库，以获取上述临床试验的最新信息。专家评论：接受靶向治疗的患者肿瘤反应迅速。然而，几乎所有患者都会对治疗产生耐药性。目前正在研究克服耐药机制的联合治疗方法。未来，靶向治疗策略可能会包括三种或更多药物，可能来自不同的治疗类别。
