Outcome of combination therapy using BRAF and MEK inhibitors among Asian patients with advanced melanoma: An analysis of 112 cases
Outcome of combination therapy using BRAF and MEK inhibitors among Asian patients with advanced melanoma: An analysis of 112 cases
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DOI：
10.1016/j.ejca.2020.12.021
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发表时间：
2021-01-24
影响因子：
8.4
通讯作者：
Yoshino, Koji
中科院分区：
文献类型：
--
作者：
Fujisawa, Yasuhiro;Ito, Takamichi;Yoshino, Koji
背景：由于大多数评估BRAF和MEK抑制剂联合治疗(B+MinH)的临床试验都是在西方国家进行的，因此对B+MinH在东亚人群中的疗效知之甚少。材料和方法：从日本16个研究所收集了B+MinH(达普拉非尼+曲美替尼或安可拉非尼+比尼美替尼)治疗晚期黑色素瘤患者的资料。结果：我们分析了收集到的144份病历中的112份，其中14份为肢端/粘膜黑色素瘤。整个队列的有效率为75.0%。肢端/粘膜黑色素瘤和皮肤黑色素瘤的有效率分别为64.3%和76.5%，差异无统计学意义(P>0.05)，而以前使用免疫检查点抑制剂(ICIS)治疗对B+MinH的有效率(72.7%和73.9%)不受影响，B+Minh后对ICI的有效率仅为20%。完全缓解的患者24个月总生存率最高(94.7%)。升高的血清乳酸脱氢酶水平和3个或更多的转移部位独立地与生存相关。最常见的复发部位是大脑(17.9%)。超过一半的患者(58.8%)出现了III/IV度发热。结论：B+MinH对日本黑色素瘤患者有效，包括肢端/粘膜黑色素瘤患者。与生存相关的因素与以前的西方研究相似。B+Minh反应不受以前使用ICI的影响；然而，在B+Minh治疗期间需要警惕脑转移，因为大脑是我们最常遇到的复发部位。(C)2020爱思唯尔有限公司。保留所有权利。
Background: 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.Material and methods: 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.Results: 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.Conclusion: 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. (C) 2020 Elsevier Ltd. All rights reserved.