Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial
Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial
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DOI：
10.1016/j.ejca.2017.08.022
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发表时间：
2017-11-01
影响因子：
8.4
通讯作者：
Hansson, J.
中科院分区：
文献类型：
--
作者：
Basset-Seguin, N.;Hauschild, A.;Hansson, J.
背景：VismodEgib研究中的SafeTy事件（STEVIE，ClinicalTrials.gov，NCT 01367665）评估了vismodegib的安全性和疗效，vismodegib是一种一流的Hedgehog通路抑制剂，在晚期基底细胞癌（BCC）中显示出临床获益，在代表临床实践的患者人群中。主要分析数据presented.Patients和方法：局部晚期或转移性基底细胞癌患者接受口服维莫德吉150 mg/d，直到疾病进展，不可接受的毒性，或退出。主要目的是安全性。疗效变量进行了评估，作为次要endpoints.Results：可评价的成人患者（N = 1215，1119局部晚期; 96转移性基底细胞癌）从36个国家进行了治疗; 147例（12%）仍在研究报告时。中位（范围）治疗持续时间为8.6（0-44）个月。大多数患者（98%）有≥ 1例治疗后出现的不良事件（TEAE）。最常见TEAE的发生率与既往分析中的报告一致。肌酸磷酸激酶（CPK）异常和肌肉痉挛之间没有相关性。289例患者（23.8%）发生严重TEAE。暴露≥ 12个月未导致新发TEAE的发生率或严重程度增加。无论Gorlin综合征状态如何，大多数在治疗中止时仍在持续的最常见TEAE均在12个月后消退。应答率（经病理学评估）有组织学证实的可测量基线疾病的患者中，（95%置信区间（CI）为65.7-71.3），局部晚期BCC患者为36.9%，（95% CI 26.6-48.1）。结论：STEVIE的主要分析表明，在临床实践中，维莫德吉在典型患者中可耐受;安全性特征与既往报告一致。长期暴露与TEAE的严重程度/频率恶化无关。研究者评估的缓解率显示肿瘤控制率高。(C)2017作者出版社：Elsevier Ltd
Background: The SafeTy Events in VIsmodEgib study (STEVIE, ClinicalTrials.gov,NCT01367665), assessed safety and efficacy of vismodegibd-a first-in-class Hedgehog pathway inhibitor demonstrating clinical benefit in advanced basal cell carcinoma (BCC)-in a patient population representative of clinical practice. Primary analysis data are presented.Patients and methods: Patients with locally advanced or metastatic BCC received oral vismodegib 150 mg/d until progressive disease, unacceptable toxicity, or withdrawal. Primary objective was safety. Efficacy variables were assessed as secondary end-points.Results: Evaluable adult patients (N = 1215, 1119 locally advanced; 96 metastatic BCC) from 36 countries were treated; 147 patients (12%) remained on study at time of reporting. Median (range) treatment duration was 8.6 (0-44) months. Most patients (98%) had >= 1 treatment-emergent adverse event (TEAE). The incidence of the most common TEAEs was consistent with reports in previous analyses. No association between creatine phosphokinase (CPK) abnormalities and muscle spasm was observed. Serious TEAEs occurred in 289 patients (23.8%). Exposure >= 12 months did not lead to increased incidence or severity of new TEAEs. The majority of the most common TEAEs ongoing at time of treatment discontinuation resolved by 12 months afterwards, regardless of Gorlin syndrome status. Response rates (investigator-assessed) in patients with histologically confirmed measurable baseline disease were 68.5% (95% confidence interval (CI) 65.7-71.3) in patients with locally advanced BCC and 36.9% (95% CI 26.6-48.1) in patients with metastatic BCC.Conclusions: The primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control. (C) 2017 The Authors. Published by Elsevier Ltd.