黑色素瘤Mekinist+Tafinlar组合疗法III期研究疗效显著提前终止（COMBI-v试验）

葛兰素史克（GSK）近日宣布，独立数据监测委员会（IDMC）已建议III期COMBI-v（MEK116513）提前终止。COMBI-v是一项III期研究，在BRAF V600E或V600K突变阳性不可切除性或转移性黑色素瘤患者中开展，调查了黑色素瘤药物Mekinist（trametinib）+ Tafinlar（dabrafenib）组合疗法相对于vemurafenib的疗效。

IDMC的积极建议，是基于COMBI-v的一项既定中期分析的积极数据。该分析数据证明，与vemurafenib相比，Mekinist+Tafinlar组合疗法在横跨既定疗效终止边界均表现出总生存期（OS）利益。进一步的疗效和安全性数据分析正在进行中，预计将在未来几个月内完成。该项研究中，vemurafenib治疗组的患者将被允许接受Mekinist+Tafinlar组合疗法治疗。

关于COMBI-v：

COMBI-v是一项随机、开放标签III期研究，在BRAF V600E或V600K突变阳性不可切除性或转移性皮肤黑色素瘤患者中开展，调查了Mekinist+Tafinlar组合疗法相对于vemurafenib的疗效。该项研究中所招募的704例患者来自美国、欧洲、加拿大、俄罗斯、乌克兰、以色列、阿根廷、巴西、韩国、新西兰、中国台湾和澳大利亚等地的研究中心。研究的主要目标是评估总生存期（OS），次要终点包括无进展生存期（PFS）、总缓解率（ORR）及缓解持续时间。

相关出处：

Dabrafenib (Tafinlar) and trametinib (Mekinist) metastatic melanoma.Med Lett Drugs Ther. 2013 Aug 5;55(1422):62-3

关于Tafinlar和Mekinist：

Tafinlar和Mekinist是GSK研发的2款黑色素瘤新药，均于2013年5月获FDA批准。Tafinlar为BRAF抑制剂，作为一种单药口服胶囊，适用于携带BRAF V600E突变的手术不可切除性黑色素瘤或转移性黑色素瘤成人患者的治疗。Mekinist为首个MEK抑制剂，作为一种单药口服片剂，适用于携带BRAF V600E或V600K突变的手术不可切除性黑色素瘤或转移性黑色素瘤成人患者的治疗。

Tafinlar不适用于野生型BRAF黑色素瘤患者的治疗。Mekinist不适用于既往接受过BRAF抑制剂疗法的患者的治疗。

转移性黑色素瘤中，约有一半携带BRAF突变，该异常突变能促使黑色素瘤生长和扩散。Tafinlar和Mekinist分别获批用于携带BRAF V600E突变的患者，该突变约占转移性黑色素瘤所有BRAF V600突变的85%。Mekinist同时获批用于携带BRAF V600K突变的患者，该突变约占转移性黑色素瘤所有BRAF V600突变的10%。

英文原文：Trametinib (Mekinist™) and dabrafenib (Tafinlar™) combination demonstrated overall survival benefit compared to vemurafenib; phase III BRAF V600-mutant metastatic melanoma study stopped early

GlaxoSmithKline plc (LSE/NYSE: GSK) announced today that the Independent Data Monitoring Committee (IDMC)  recommended COMBI-v (MEK116513), a phase III study of its MEK inhibitor, trametinib (Mekinist™), in combination with its BRAF inhibitor, dabrafenib (Tafinlar™), compared to vemurafenib in patients with BRAF V600E or V600K mutation-positive unresectable or metastatic cutaneous melanoma be stopped early. This IDMC recommendation is based on an interim analysis which demonstrated an overall survival benefit for the trametinib and dabrafenib combination compared to vemurafenib that crossed the pre-specified efficacy stopping boundary. The safety profile of the trametinib and dabrafenib arm was consistent with the safety profile of the combination observed to date.

The IDMC recommendation today is based on headline data; further analysis of safety and efficacy data is underway and will be completed in the coming months. Eligible study patients who were randomised to the vemurafenib arm will be allowed to cross over to receive treatment with the trametinib and dabrafenib combination.

Dr. Rafael Amado, Head of Oncology R&D at GSK, said: “Today’s headline results for the combination of dabrafenib and trametinib add to the body of evidence our phase III program has provided thus far, which we hope will more fully characterise the efficacy and safety profile of this combination for patients with BRAF V600-mutant metastatic melanoma. We will continue to analyse this data versus vemurafenib over the coming months and look forward to sharing these with the scientific community once the analysis is complete.” 

About COMBI-v

This phase III, randomised, open-label study compared the combination of dabrafenib and trametinib to vemurafenib in subjects with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma. COMBI-v enrolled 704 patients from investigative sites in the U.S., Europe, Canada, Russia, Ukraine, Israel, Argentina, Brazil, Korea, New Zealand, Taiwan, and Australia.

The primary objective of the study was to evaluate dabrafenib and trametinib combination therapy vs. vemurafenib with respect to OS. Secondary objectives evaluated and compared dabrafenib and trametinib combination therapy versus vemurafenib with respect to progression-free survival, overall response rate, and duration of response. The safety of dabrafenib and trametinib combination therapy, including incidences of squamous cell carcinoma and other proliferative skin diseases, was also evaluated.