COLUMBUS 研究中耐受性和总生存期更新：随机 3 期试验中比较 encorafenib 加 binimetinib 与 vemurafenib 或 encorafenib 治疗 BRAF V600 突变型黑色素瘤患者的里程碑分析结果
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.
机构信息
Melanoma Unit, Cancer Immunotherapy and Innovative Therapies, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy.
Department of Dermatology, University Hospital Zürich Skin Cancer Center and University Zürich, Zürich, Switzerland.
出版信息
Eur J Cancer. 2020 Feb;126:33-44. doi: 10.1016/j.ejca.2019.11.016. Epub 2020 Jan 2.
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.
背景
BRAF/MEK 抑制剂联合治疗已被证实可改善 BRAF V600 突变型黑色素瘤患者的无进展生存期（PFS）和总生存期（OS），成为 BRAF V600 突变型不可切除皮肤癌的标准治疗方法。在此，我们报告 COLUMBUS （COmbined LGX818 [encorafenib] Used with MEK162 [binimetinib] in BRAF mutant Unresectable Skin cancer）试验的长期随访更新分析结果。
方法
在 COLUMBUS 试验的第 1 部分中，577 例未经治疗或一线免疫治疗后进展的晚期/转移性 BRAF V600 突变型黑色素瘤患者以 1:1:1 的比例随机分配至每日一次口服 450mg 恩考芬尼+每日两次口服 45mg 比美替尼（COMBO450）组、每日两次口服 960mg 维莫非尼（VEM）组或每日一次口服 300mg 恩考芬尼（ENCO300）组。本次更新分析纳入了 PFS、OS、客观缓解率、安全性和耐受性，并对预后亚组的结果进行了分析。
结果
截止数据截点，COMBO450、ENCO300 和 VEM 治疗组的死亡人数分别为 116、113 和 138 例。COMBO450 组的中位 OS 为 33.6 个月（95%CI，24.4-39.2），ENCO300 组为 23.5 个月（95%CI，19.6-33.6），VEM 组为 16.9 个月（95%CI，14.0-24.5）。与 VEM 相比，COMBO450 降低了 39%的死亡风险（HR，0.61；95%CI，0.48-0.79）。COMBO450 的中位更新 PFS 为 14.9 个月（95%CI，11.0-20.2），ENCO300 为 9.6 个月（95%CI，7.4-14.8），VEM 为 7.3 个月（95%CI，5.6-7.9）。与 VEM 相比，COMBO450 组的 PFS 更长（HR，0.51；95%CI，0.39-0.67）。里程碑式的 OS 和 PFS 结果显示，每年分析的结果均一致。各亚组均显示 COMBO450 优于 VEM。
结论
COLUMBUS 试验中 COMBO450 的更新 PFS 和 OS 结果表明，该方案可为晚期 BRAF V600 突变型黑色素瘤患者带来长期获益。
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