Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma
Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma
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DOI：
10.1056/nejmoa1408868
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发表时间：
2014-11-13
影响因子：
158.5
通讯作者：
Ribas, Antoni
中科院分区：
文献类型：
--
作者：
Larkin, James;Ascierto, Paolo A.;Ribas, Antoni
背景：BRAF和MEK的联合抑制被认为可以通过预防或延缓单独使用BRAF抑制剂观察到的耐药性的出现来改善黑色素瘤患者的临床预后。这项随机的3期研究评估了BRAF抑制剂Vemurafenib和MEK抑制剂Cobimetinib的组合。方法：我们随机将495名之前未经治疗、无法切除的局部晚期或转移性BRAF V600突变阳性黑色素瘤患者随机分配到维莫拉非尼和Cobimetinib(联合组)或vemurafenib和安慰剂(对照组)。结果联合组的中位无进展生存期为9.9个月，对照组为6.2个月(死亡或疾病进展的危险比为0.51；95%可信区间[CI]为0.39~0.68；P
BACKGROUNDThe combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes in patients with melanoma by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib.METHODSWe randomly assigned 495 patients with previously untreated unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma to receive vemurafenib and cobimetinib (combination group) or vemurafenib and placebo (control group). The primary end point was investigator-assessed progression-free survival.RESULTSThe median progression-free survival was 9.9 months in the combination group and 6.2 months in the control group (hazard ratio for death or disease progression, 0.51; 95% confidence interval [CI], 0.39 to 0.68; P