Department of Dermatology, University of Tsukuba, Japan.
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Japan.
Eur J Cancer. 2021 Mar;145:210-220. doi: 10.1016/j.ejca.2020.12.021. Epub 2021 Jan 24.
As most clinical trials evaluating BRAF and MEK inhibitor combination therapy (B + Minh) have been conducted in Western countries, little is known about the effect of B + Minh among East Asian populations.
Data from patients with advanced melanoma treated using B + Minh (either dabrafenib + trametinib or encorafenib + binimetinib) were retrospectively collected from 16 institutes in Japan. Response rates, adverse events, patterns of failure and survival were analysed.
We analysed 112 of 144 collected patient records and, of these, 14 had acral/mucosal melanoma. The response rate for the entire cohort was 75.0%. There were no statistical differences in response rates between acral/mucosal and cutaneous melanomas (64.3% versus 76.5%), whereas previous treatment using immune checkpoint inhibitors (ICIs) did not affect response (72.7% versus 73.9%) to B + Minh, response to ICI after B + Minh was only 20%. Patients who achieved complete response had the best overall survival rates at 24 months (94.7%). Elevated serum lactate dehydrogenase levels and 3 or more metastatic sites were independently associated with survival. The most common relapse site was the brain (17.9%). More than half of the patients (58.8%) experienced grade III/IV pyrexia.
B + Minh was effective among Japanese patients with melanoma, including those with acral/mucosal melanoma. Factors associated with survival were similar to previous Western studies. B + Minh response was not affected by the previous use of ICI; however, vigilance against brain metastasis during B + Minh therapy is required as the brain was our most commonly encountered relapse site.
由于大多数评估 BRAF 和 MEK 抑制剂联合治疗（B + M）的临床试验都是在西方国家进行的，因此对于东亚人群中 B + M 的疗效知之甚少。
从日本 16 家医院回顾性收集了接受 B + M（达布拉非尼 + 曲美替尼或恩考芬尼 + 比美替尼）治疗的晚期黑色素瘤患者的数据。分析了缓解率、不良反应、失败模式和生存情况。
我们分析了收集到的 144 份患者记录中的 112 份，其中 14 份为肢端/黏膜黑色素瘤。全队列的缓解率为 75.0%。肢端/黏膜和皮肤黑色素瘤的缓解率无统计学差异（64.3%与 76.5%），而 B + M 之前使用免疫检查点抑制剂（ICI）并不影响其反应（72.7%与 73.9%），B + M 后对 ICI 的反应仅为 20%。达到完全缓解的患者 24 个月的总生存率最佳（94.7%）。血清乳酸脱氢酶水平升高和 3 个或更多转移部位与生存相关。最常见的复发部位是大脑（17.9%）。超过一半的患者（58.8%）发生 3 级/4 级发热。
B + M 对日本黑色素瘤患者有效，包括肢端/黏膜黑色素瘤患者。与既往西方研究相似，生存相关因素。B + M 之前使用 ICI 不影响其反应；然而，在 B + M 治疗期间需要警惕脑转移，因为大脑是我们最常见的复发部位。
