Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Department of Dermatologic Oncology, National Cancer Center Hospital East, Chiba, Japan.
J Dermatol. 2024 Sep;51(9):1199-1207. doi: 10.1111/1346-8138.17263. Epub 2024 May 8.
Most clinical trials investigating targeted therapies for patients harboring BRAF V600 mutations have included mostly White patients, and data for Asian patients are scarce. Although there are several retrospective studies in Japanese patients, they have investigated only the dabrafenib + trametinib regimen, and have had a short follow-up period. We conducted a single-center retrospective study to update previous studies and compare the outcomes with those in White patients. We analyzed 89 patients who received dabrafenib + trametinib or encorafenib + binimetinib, including 11 who received both treatment regimens. The overall response rate was 79.8%, with complete response in 25 patients (28.1%) and partial response in 45 patients (51.7%). The median progression-free survival was 13.7 months, and the median overall survival was 32.9 months. The 3-year progression-free and overall survival rates were 31.8% and 47.9%, respectively. Although the two regimens showed no significant differences in efficacy, their safety profiles differed, as reported in clinical trials. Therefore, the most frequent adverse event associated with the dabrafenib + trametinib regimen was pyrexia (61.3%) and that of encorafenib + binimetinib was blurred vision (32.0%). Switching directly to another targeted therapy after progressive disease showed no clinical response; however, rechallenge followed by immune checkpoint inhibitor therapy showed a certain response. As a prognostic factor, performance status was associated with progression-free survival, and performance status, serum lactate dehydrogenase level, and dose interruption were associated with overall survival in the multivariate analysis. Real-world data on targeted therapy for patients with melanoma in Japan suggest that both dabrafenib + trametinib and encorafenib + binimetinib show similar efficacy and safety in Asian and White patients.
大多数针对携带 BRAF V600 突变患者的靶向治疗的临床试验主要纳入了白人患者，亚洲患者的数据很少。虽然有几项针对日本患者的回顾性研究，但它们仅调查了 dabrafenib + trametinib 方案，且随访时间较短。我们进行了一项单中心回顾性研究，以更新之前的研究，并将结果与白人患者进行比较。我们分析了 89 名接受 dabrafenib + trametinib 或 encorafenib + binimetinib 治疗的患者，包括 11 名接受两种治疗方案的患者。总体缓解率为 79.8%，完全缓解 25 例（28.1%），部分缓解 45 例（51.7%）。中位无进展生存期为 13.7 个月，中位总生存期为 32.9 个月。3 年无进展生存率和总生存率分别为 31.8%和 47.9%。虽然两种方案在疗效上无显著差异，但它们的安全性特征与临床试验报告的不同。因此，dabrafenib + trametinib 方案最常见的不良反应是发热（61.3%），encorafenib + binimetinib 方案是视力模糊（32.0%）。疾病进展后直接切换至另一种靶向治疗无临床反应；然而，重新使用免疫检查点抑制剂治疗有一定反应。作为预后因素，在多变量分析中，表现状态与无进展生存期相关，表现状态、血清乳酸脱氢酶水平和剂量中断与总生存期相关。日本黑色素瘤患者靶向治疗的真实世界数据表明，dabrafenib + trametinib 和 encorafenib + binimetinib 在亚洲和白人患者中均显示出相似的疗效和安全性。
