Encorafenib + binimetinib和vemurafenib Encorafenib BRAF-mutant黑色素瘤患者(哥伦布):一项多中心、非盲、随机3期临床试验。

文章的细节

引用
复制到剪贴板

dum R, Ascierto PA、Gogas HJ Arance,曼荼罗M, Liszkay G, Garbe C, Schadendorf D, Krajsova我Gutzmer R, Chiarion-Sileni V, Dutriaux C, de Groot JWB,山崎N, Loquai C, Moutouh-de帕拉,皮卡德医学博士,桑德尔V, Flaherty KT罗伯特·C

Encorafenib + binimetinib和vemurafenib Encorafenib BRAF-mutant黑色素瘤患者(哥伦布):一项多中心、非盲、随机3期临床试验。

柳叶刀杂志。2018;19 (5):603 - 615。doi: 10.1016 / s1470 - 2045 (18) 30142 - 6。Epub 2018年3月21日。

PubMed ID
29573941 (在PubMed
]
文摘

背景:联合BRAF-MEK抑制剂治疗照顾BRAF的标准(V600)突变先进的黑色素瘤。我们调查了encorafenib BRAF抑制剂具有独特的约束性目标属性,单独或结合MEK抑制剂binimetinib,与晚期患者的vemurafenib BRAF突变黑色素瘤(V600)。方法:哥伦布是两部分,进行随机、非盲3期研究在28个国家的162家医院。符合条件的患者18岁或以上,组织学证实局部晚期(美国癌症联合委员会希望(与)阶段,IIIC,或IV),不可切除或转移性皮肤的黑色素瘤,或未知的原发性黑色素瘤;一个BRAF V600E)或BRAF突变(V600K);东部合作肿瘤组(ECOG) 0或1的性能状态;,之前或之后的一线治疗天真或已经进行免疫治疗。在第1部分的研究中,患者被随机分配(比)通过互动响应技术接受口服encorafenib 450毫克每天一次+口服binimetinib 45毫克(encorafenib + binimetinib集团),每日两次口服encorafenib 300毫克每日一次(encorafenib组),或口头vemurafenib 960毫克每天两次(vemurafenib组)。失明的主要终点是无进展生存独立的中央审查encorafenib + binimetinib与vemurafenib。功效由意向处理分析。 Safety was analysed in patients who received at least one dose of study drug and one postbaseline safety assessment. The results of part 2 will be published separately. This study is registered with ClinicalTrials.gov, number NCT01909453, and EudraCT, number 2013-001176-38. FINDINGS: Between Dec 30, 2013, and April 10, 2015, 577 of 1345 screened patients were randomly assigned to either the encorafenib plus binimetinib group (n=192), the encorafenib group (n=194), or the vemurafenib group (n=191). With a median follow-up of 16.6 months (95% CI 14.8-16.9), median progression-free survival was 14.9 months (95% CI 11.0-18.5) in the encorafenib plus binimetinib group and 7.3 months (5.6-8.2) in the vemurafenib group (hazard ratio [HR] 0.54, 95% CI 0.41-0.71; two-sided p<0.0001). The most common grade 3-4 adverse events seen in more than 5% of patients in the encorafenib plus binimetinib group were increased gamma-glutamyltransferase (18 [9%] of 192 patients), increased creatine phosphokinase (13 [7%]), and hypertension (11 [6%]); in the encorafenib group they were palmoplantar erythrodysaesthesia syndrome (26 [14%] of 192 patients), myalgia (19 [10%]), and arthralgia (18 [9%]); and in the vemurafenib group it was arthralgia (11 [6%] of 186 patients). There were no treatment-related deaths except for one death in the combination group, which was considered possibly related to treatment by the investigator. INTERPRETATION: Encorafenib plus binimetinib and encorafenib monotherapy showed favourable efficacy compared with vemurafenib. Overall, encorafenib plus binimetinib appears to have an improved tolerability profile compared with encorafenib or vemurafenib. Encorafenib plus binimetinib could represent a new treatment option for patients with BRAF-mutant melanoma. FUNDING: Array BioPharma, Novartis.

DrugBank数据引用了这篇文章

药物
药物靶点
药物 目标 类 生物 药理作用 行动
Encorafenib G1 / S-specific周期蛋白d1 蛋白质 人类
是的
抑制剂
 细节