U.S. Food and Drug Administration Approval: Vismodegib for Recurrent, Locally Advanced, or Metastatic Basal Cell Carcinoma
U.S. Food and Drug Administration Approval: Vismodegib for Recurrent, Locally Advanced, or Metastatic Basal Cell Carcinoma
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DOI：
10.1158/1078-0432.ccr-12-1956
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发表时间：
2013-05-01
影响因子：
11.5
通讯作者：
Pazdur, Richard
中科院分区：
文献类型：
--
作者：
Axelson, Michael;Liu, Ke;Pazdur, Richard
本文描述了导致美国食品药品监督管理局（FDA）于2012年1月30日批准Erivedge（维莫德吉）胶囊用于治疗复发性、局部晚期或转移性基底细胞癌（BCC）患者的数据和监管考虑。FDA的批准决定主要基于在一项单臂，平行队列，国际试验中观察到的结果，该试验在病理证实的复发性局部晚期基底细胞癌（laBCC）或转移性基底细胞癌（mBCC）患者中每天口服150 mg，直至疾病进展。一个独立审查委员会证实，33例mBCC患者的总缓解率（ORR）为30.3% [95%置信区间（CI）：15.6-48.2]，63例laBCC患者的ORR为42.9%（95% CI：30.5-56.0）; mBCC和laBCC患者的中位缓解持续时间分别为7.6个月和7.6个月。最常见的不良反应为肌肉痉挛、脱发、味觉障碍、体重减轻、疲乏、恶心、腹泻、食欲下降、便秘、咳嗽、关节痛、呕吐、头痛、味觉丧失、失眠和上呼吸道感染。动物毒理学研究证实，维莫德吉是一种有效的致畸剂。批准是基于持久的客观肿瘤缓解，这是由Hedgehog信号传导在BCC中的病理作用的知识和在没有有效替代疗法的人群中可接受的毒性支持的。(c)2013年AACR。
The data and regulatory considerations leading to the U.S. Food and Drug Administration (FDA) January 30, 2012 approval of Erivedge (vismodegib) capsules for the treatment of patients with recurrent, locally advanced, or metastatic basal cell carcinoma (BCC) are described. The FDA's approval decision was based primarily on the results observed in a single-arm, parallel cohort, international trial of vismodegib, administered orally at 150 mg daily until disease progression, in patients with pathologically confirmed, recurrent, locally advanced basal cell carcinoma (laBCC) or metastatic basal cell carcinoma (mBCC). An independent review committee confirmed an overall response rate (ORR) of 30.3% [95% confidence interval (CI): 15.6-48.2] in 33 patients with mBCC and an ORR of 42.9% (95% CI: 30.5-56.0) in 63 patients with laBCC; median response durations were 7.6 months and 7.6 months for patients with mBCC and laBCC, respectively. The most common adverse reactions were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, cough, arthralgias, vomiting, headache, ageusia, insomnia, and upper respiratory tract infection. Animal toxicology studies confirmed that vismodegib is a potent teratogenic agent. Approval was based on durable objective tumor responses supported by knowledge of the pathologic role of Hedgehog signaling in BCC and acceptable toxicity in a population without effective alternative therapies. (c) 2013 AACR.