Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma
Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma
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DOI：
10.1016/j.ejca.2019.11.016
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发表时间：
2020-02-01
影响因子：
8.4
通讯作者：
Robert, Caroline
中科院分区：
文献类型：
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作者：
Ascierto, Paolo A.;Dummer, Reinhard;Robert, Caroline
背景：BRAF/MEK抑制剂组合是基于BRAF V600突变黑色素瘤在无进展生存期(PFS)和总生存期(OS)方面的优势而确立的治疗方法。在哥伦布试验的第一部分中，577名未经治疗或在一线免疫治疗后进展的晚期/转移性BRAF V600突变黑色素瘤患者被随机分为1：1：1：1至450 mg的恩可拉非尼qd+45 mg的binimetinib Bid(COMBO450)与960 mg的vemurafenib(VEM)或300 mg的encorafenib ENCO QD(CO300)。结果：截止数据时，COMBO450、ENCO300和VEM治疗组分别有116、113和138例死亡。COMBO450、ENCO300和VEM的中位OS分别为33.6个月(95%可信区间，24.4-39.2)、23.5个月(95%可信区间，19.6-33.6)和16.9个月(95%可信区间，14.0-24.5)。与VEM相比，COMBO450降低了39%的死亡风险(危险比[HR]，0.61；95%CI，0.48-0.79)。COMBO450组、ENCO300组和VEM组的中位PFS分别为14.9个月(95%CI，11.0-20.2)、9.6个月(95%CI，7.4-14.8)和7.3个月(95%CI，5.6-7.9)。COMBO450组较VEM组PFS更长(HR，0.51；95%CI，0.39~0.67)。里程碑OS和PFS的结果显示了分析的每一年的一致结果。亚组均支持COMBO450与VEM。结论：COMBO450在Columbus试验中的最新PFS和OS结果显示，COMBO450对晚期BRAF V600突变黑色素瘤患者有长期益处。(C)2019年提交人。爱思唯尔有限公司出版。
Background: BRAF/MEK inhibitor combinations are established treatments for BRAF V600-mutant melanoma based on demonstrated benefits on progression-free survival (PFS) and overall survival (OS). Here, we report an updated analysis of the COLUMBUS (COmbined LGX818 [encorafenib] Used with MEK162 [binimetinib] in BRAF mutant Unresectable Skin cancer) trial with long-term follow-up.Methods: In part 1 of the COLUMBUS trial, 577 patients with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomised 1:1:1 to 450 mg of encorafenib QD + 45 mg of binimetinib BID (COMBO450) vs 960 mg of vemurafenib BID (VEM) or 300 mg of encorafenib ENCO QD (ENCO300). An updated analysis was conducted that included PFS, OS, objective response rate, safety and tolerability and analyses of results by prognostic subgroups.Results: At data cutoff, there were 116, 113 and 138 deaths in the COMBO450, ENCO300 and VEM treatment arms, respectively. The median OS was 33.6 months (95% confidence interval [CI], 24.4-39.2) for COMBO450, 23.5 months (95% CI, 19.6-33.6) for ENCO300 and 16.9 months (95% CI, 14.0-24.5) for VEM. Compared with VEM, COMBO450 decreased the risk of death by 39% (hazard ratio [HR], 0.61; 95% CI, 0.48-0.79). The updated median PFS for COMBO450 was 14.9 months (95% CI, 11.0-20.2), ENCO300 was 9.6 months (95% CI, 7.4-14.8) and VEM was 7.3 months (95% CI, 5.6-7.9). PFS was longer for COMBO450 vs VEM (HR, 0.51; 95% CI, 0.39-0.67). Landmark OS and PFS results show consistent results for each year analysed. Subgroups all favoured COMBO450 vs VEM.Conclusions: Updated PFS and OS results for COMBO450 from the COLUMBUS trial demonstrate a long-term benefit in patients with advanced BRAF V600-mutated melanoma. (C) 2019 The Authors. Published by Elsevier Ltd.