Basset-Séguin N, Hauschild A, Kunstfeld R, Grob J, Dréno B, Mortier L, Ascierto P A, Licitra L, Dutriaux C, Thomas L, Meyer N, Guillot B, Dummer R, Arenberger P, Fife K, Raimundo A, Dika E, Dimier N, Fittipaldo A, Xynos I, Hansson J
Department of Dermatology, Hôpital Saint Louis, 1 Avenue Claude Vellefaux, 75475, Paris, France.
Department of Dermatology, University of Kiel, Rosalind-Franklin-Str 7, D-24105, Kiel, Germany.
Eur J Cancer. 2017 Nov;86:334-348. doi: 10.1016/j.ejca.2017.08.022. Epub 2017 Nov 5.
The SafeTy Events in VIsmodEgib study (STEVIE, ClinicalTrials.gov, NCT01367665), assessed safety and efficacy of vismodegib-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 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.
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.
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. CLINICALTRIALS.GOV: NCT01367665.
维莫德吉安全性事件研究（STEVIE，ClinicalTrials.gov，NCT01367665），在一个代表临床实践的患者群体中，评估了维莫德吉（一种一流的Hedgehog通路抑制剂，在晚期基底细胞癌（BCC）中显示出临床益处）的安全性和有效性。现公布主要分析数据。
局部晚期或转移性BCC患者口服维莫德吉150mg/天，直至疾病进展、出现不可接受的毒性或停药。主要目标是安全性。疗效变量作为次要终点进行评估。
来自36个国家的可评估成年患者（N = 1215，1119例局部晚期；96例转移性BCC）接受了治疗；报告时147例患者（12%）仍在研究中。中位（范围）治疗持续时间为8.6（0 - 44）个月。大多数患者（98%）发生≥1次治疗中出现的不良事件（TEAE）。最常见TEAE的发生率与先前分析中的报告一致。未观察到肌酸磷酸激酶（CPK）异常与肌肉痉挛之间存在关联。289例患者（23.8%）发生严重TEAE。暴露≥12个月未导致新TEAE的发生率或严重程度增加。无论是否患有戈林综合征，大多数在治疗中断时仍存在的最常见TEAE在之后12个月内得到缓解。组织学确诊有可测量基线疾病的患者中，局部晚期BCC患者的缓解率（研究者评估）为68.5%（95%置信区间（CI）65.7 - 71.3），转移性BCC患者为36.9%（95%CI 26.6 - 48.1）。
STEVIE的主要分析表明，维莫德吉在临床实践中的典型患者中耐受性良好；安全性概况与先前报告一致。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出较高的肿瘤控制率。临床试验注册编号：NCT01367665。
