University Hospital Zurich, Zurich, Switzerland.
Massachusetts General Hospital, Boston, MA.
J Clin Oncol. 2022 Dec 20;40(36):4178-4188. doi: 10.1200/JCO.21.02659. Epub 2022 Jul 21.
Combination treatment with BRAF and MEK inhibitors has demonstrated benefits on progression-free survival (PFS) and overall survival (OS) and is a standard of care for the treatment of advanced V600-mutant melanoma. Here, we report the 5-year update from the COLUMBUS trial (ClinicalTrials.gov identifier: NCT01909453).
Patients with locally advanced unresectable or metastatic V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomly assigned 1:1:1 to encorafenib 450 mg once daily plus binimetinib 45 mg twice daily, vemurafenib 960 mg twice daily, or encorafenib 300 mg once daily. An updated analysis was conducted 65 months after the last patient was randomly assigned.
Five hundred seventy-seven patients were randomly assigned: 192 to encorafenib plus binimetinib, 191 to vemurafenib, and 194 to encorafenib. The 5-year PFS and OS rates with encorafenib plus binimetinib were 23% and 35% overall and 31% and 45% in those with normal lactate dehydrogenase levels, respectively. In comparison, the 5-year PFS and OS rates with vemurafenib were 10% and 21% overall and 12% and 28% in those with normal lactate dehydrogenase levels, respectively. The median duration of response with encorafenib plus binimetinib was 18.6 months, with disease control achieved in 92.2% of patients. In comparison, the median duration of response with vemurafenib was 12.3 months, with disease control achieved in 81.2% of patients. Long-term follow-up showed no new safety concerns, and results were consistent with the known tolerability profile of encorafenib plus binimetinib. Interactive visualization of the data presented in this article is available at COLUMBUS dashboard.
In this 5-year update of part 1 of the COLUMBUS trial, encorafenib plus binimetinib treatment demonstrated continued long-term benefits and a consistent safety profile in patients with V600-mutant melanoma.
BRAF 和 MEK 抑制剂联合治疗已显示出对无进展生存期（PFS）和总生存期（OS）的益处，是治疗晚期 V600 突变型黑色素瘤的标准治疗方法。在这里，我们报告了 COLUMBUS 试验的 5 年更新结果（ClinicalTrials.gov 标识符：NCT01909453）。
局部晚期不可切除或转移性 V600 突变型黑色素瘤患者，未经治疗或一线免疫治疗后进展，按 1:1:1 随机分配至恩考芬尼 450mg 每日一次加比美替尼 45mg 每日两次、维莫非尼 960mg 每日两次或恩考芬尼 300mg 每日一次。在最后一名患者随机分配后 65 个月进行了更新分析。
577 名患者被随机分配：192 名接受恩考芬尼加比美替尼治疗，191 名接受维莫非尼治疗，194 名接受恩考芬尼治疗。恩考芬尼加比美替尼治疗的 5 年 PFS 和 OS 率分别为总体 23%和 35%，乳酸脱氢酶正常者分别为 31%和 45%。相比之下，维莫非尼治疗的 5 年 PFS 和 OS 率分别为总体 10%和 21%，乳酸脱氢酶正常者分别为 12%和 28%。恩考芬尼加比美替尼治疗的中位缓解持续时间为 18.6 个月，92.2%的患者疾病得到控制。相比之下，维莫非尼治疗的中位缓解持续时间为 12.3 个月，81.2%的患者疾病得到控制。长期随访未发现新的安全性问题，结果与恩考芬尼加比美替尼已知的可耐受性一致。本文数据的交互可视化可在 COLUMBUS 仪表板上查看。
在 COLUMBUS 试验第 1 部分的 5 年更新中，恩考芬尼加比美替尼治疗为 V600 突变型黑色素瘤患者带来了持续的长期获益和一致的安全性。
