Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies

被引：65

作者：

Gibney, Geoffrey T. ^{[1
]}

Zager, Jonathan S. ^{[1
]}

机构：

[1] H Lee Moffitt Canc Ctr & Res Inst, Dept Cutaneous Oncol, Tampa, FL 33612 USA

来源：

EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY | 2013年 / 9卷 / 07期

关键词：

BRAF inhibitor; dabrafenib; GSK2118436; melanoma; PHASE-III; METASTATIC MELANOMA; IMPROVED SURVIVAL; MEK INHIBITION; OPEN-LABEL; MUTATIONS; DACARBAZINE; CANCER; MULTICENTER; RESISTANCE;

D O I：

10.1517/17425255.2013.794220

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Introduction: The development of selective BRAF inhibitors in patients with metastatic BRAF V600 mutant melanoma has proven to be an effective therapeutic strategy. While vemurafenib was the first approved BRAF inhibitor for this indication, another selective BRAF inhibitor, dabrafenib, has demonstrated efficacy in patients with BRAF mutant melanoma, including those with active brain metastases and other malignancies. Areas covered: This review covers the current role of BRAF inhibitors in patients with metastatic melanoma and the clinical development of dabrafenib. The pharmacological, safety and efficacy data are discussed from the Phases I, II and III studies of dabrafenib. In addition, the results of the Phase II study of dabrafenib in melanoma patients with active brain metastases (BREAK-MB) and the Phase I/II study of dabrafenib/trametinib are examined. Expert opinion: While dabrafenib has demonstrated comparable efficacy to vemurafenib in BRAF V600E mutant melanoma patients, the BREAK-MB and dabrafenib/trametinib studies have taken BRAF inhibitor strategies further with evidence of disease activity in patients with metastatic melanoma brain metastases and potential abrogation of BRAF inhibitor resistance.

引用

页码：893 / 899

页数：7

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