Lineberger Comprehensive Cancer Center and North Carolina Cancer Hospital, College of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Ann Pharmacother. 2011 Nov;45(11):1399-405. doi: 10.1345/aph.1Q363. Epub 2011 Oct 25.
To summarize the preclinical and clinical data on vemurafenib, approved by the Food and Drug Administration (FDA) on August 17, 2011, and discuss the drug's clinical advantages and limitations.
An English-language literature search of MEDLINE/PubMed (1966-August 2011), using the terms PLX4032, RG7204, RO5185426, vemurafenib, and metastatic melanoma, was conducted. In addition, information and data were obtained from meeting abstracts, clinical trial registries, and news releases from the FDA.
All relevant published articles and abstracts on vemurafenib were included. Clinical trial registries and meeting abstracts were used to obtain information regarding ongoing trials. All peer-reviewed articles containing information regarding the clinical safety and efficacy of vemurafenib were evaluated for inclusion.
Before the recent approval (March 2011) of ipilimumab, there was no first-line standard-of-care therapy, with proven overall survival benefit, for the treatment of malignant metastatic melanoma. Unlike ipilimumab, which acts through immune-modulation, vemurafenib is a novel, molecularly targeted therapeutic with preferential efficacy toward a specific mutated oncogenic BRAF-signaling mediator. In recently published results of a Phase 3 clinical trial comparing dacarbazine with vemurafenib, vemurafenib prolonged progression-free and overall survival, with confirmed objective response rate of 48% (95% CI 42 to 55) versus 5% (95% CI 3 to 9) for patients who received dacarbazine (p < 0.001).
Vemurafenib offers a novel, first-line, personalized therapy for patients who have mutated BRAF. Clinical trials of vemurafenib in combination with ipilimumab or other targeted or cytotoxic chemotherapeutic agents may provide more effective regimens with long-term clinical benefit.
总结 2011 年 8 月 17 日美国食品和药物管理局（FDA）批准的 vemurafenib 的临床前和临床数据，并讨论该药的临床优势和局限性。
使用术语 PLX4032、RG7204、RO5185426、vemurafenib 和转移性黑色素瘤，对 MEDLINE/PubMed（1966 年-2011 年 8 月）进行了英文文献检索。此外，还从 FDA 的会议摘要、临床试验注册处和新闻稿中获取了信息和数据。
纳入所有关于 vemurafenib 的相关已发表文章和摘要。临床试验注册处和会议摘要用于获取正在进行的试验信息。所有包含 vemurafenib 临床安全性和疗效信息的同行评审文章均被评估是否纳入。
在 ipilimumab 最近获批（2011 年 3 月）之前，对于治疗恶性转移性黑色素瘤，尚无经证实具有总体生存获益的一线标准治疗方法。与通过免疫调节起作用的 ipilimumab 不同，vemurafenib 是一种新型的、靶向分子的治疗药物，对特定的突变致癌 BRAF 信号转导介质具有优先疗效。在一项比较达卡巴嗪与 vemurafenib 的 3 期临床试验的最新结果中，vemurafenib 延长了无进展生存期和总生存期，接受达卡巴嗪治疗的患者客观缓解率为 48%（95%CI 42 至 55），而 5%（95%CI 3 至 9）（p <0.001）。
vemurafenib 为 BRAF 突变患者提供了一种新型的一线个体化治疗方法。vemurafenib 联合 ipilimumab 或其他靶向或细胞毒性化疗药物的临床试验可能会提供更有效的方案，带来长期的临床获益。
