恩科拉非尼加比尼美替尼 (EB) 是晚期 BRAFV600 突变黑色素瘤的标准护理治疗。我们评估了 encorafenib 加 binimetinib 对 BRAFV600 突变黑色素瘤和脑转移 (BM) 患者的疗效和安全性，并探讨放疗是否可以延长缓解持续时间。E-BRAIN/GEM1802 是一项前瞻性、多中心、单组 II 期试验，入组患有 BRAFV600 突变型黑色素瘤和 BM 的患者。患者接受 encorafenib 450 mg 每天一次加 binimetinib 45 mg BID，那些在第一次肿瘤评估时获得部分缓解或疾病稳定的患者接受放射治疗。治疗持续直至疾病进展。主要终点是 EB 2 个月后的颅内缓解率 (icRR)，建立 60% 的无效阈值。该研究包括 25 名没有 BM 症状的患者和 23 名有 BM 症状的患者，无论是否使用皮质类固醇。其中，31例（64.6%）患者接受序贯放疗。两个月后，icRR 为 70.8%（95% CI：55.9-83.1）； 10.4% 完成回复。中位颅内 PFS 和 OS 分别为 8.5 (95% CI: 6.4-11.8) 和 15.9 (95% CI: 10.7-21.4) 个月（icPFS 为 8.3 个月，接受 RDT 的患者 OS 为 13.9 个月）。最常见的 3-4 级治疗相关不良事件是丙氨酸氨基转移酶 (ALT) 升高 (10.4%)。恩科拉非尼加 binimetinib 在 icRR 方面显示出有希望的临床益处，并且在高级别 TRAE 发生频率较低的情况下具有可耐受的安全性。 BRAFV600 突变黑色素瘤和 BM，包括有症状和需要类固醇的患者。序贯放疗是可行的，但似乎不会延长反应时间。© 作者 2024。由牛津大学出版社代表神经肿瘤学会出版。

Encorafenib plus binimetinib (EB) is a standard of care treatment for advanced BRAFV600-mutant melanoma. We assessed efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response.E-BRAIN/GEM1802 was a prospective, multicenter, single arm, phase II trial that enrolled patients with melanoma BRAFV600-mutant and BM. Patients received encorafenib 450 mg once daily plus binimetinib 45 mg BID, and those who achieved partial response or stable disease at first tumor assessment were offered radiotherapy. Treatment continued until progression.Primary endpoint was intracranial response rate (icRR) after 2 months of EB, establishing a futility threshold of 60%.The study included 25 patients with no BM symptoms and 23 patients with BM symptoms regardless of using corticosteroids. Among them, 31 patients (64.6%) received sequential radiotherapy. After two months, icRR was 70.8% (95% CI: 55.9-83.1); 10.4% complete response. Median intracranial PFS and OS were 8.5 (95% CI: 6.4-11.8) and 15.9 (95% CI: 10.7-21.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grade 3-4 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%).Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.