维莫德吉用于局部晚期基底细胞癌的新辅助治疗：一项多中心、开放标签的2期试验（VISMONEO研究）的初步结果：维莫德吉用于局部晚期基底细胞癌的新辅助治疗
Vismodegib in neoadjuvant treatment of locally advanced basal cell carcinoma: First results of a multicenter, open-label, phase 2 trial (VISMONEO study): Neoadjuvant Vismodegib in Locally Advanced Basal Cell Carcinoma.
作者信息
Bertrand Nicolas, Guerreschi Pierre, Basset-Seguin Nicole, Saiag Philippe, Dupuy Alain, Dalac-Rat Sophie, Dziwniel Véronique, Depoortère César, Duhamel Alain, Mortier Laurent
机构信息
Univ. Lille, CHU Lille, Oncology Department, Lille, France.
Univ. Lille, CHU Lille, Plastic and Reconstructive Surgery Department, Lille, France.
出版信息
EClinicalMedicine. 2021 Apr 26;35:100844. doi: 10.1016/j.eclinm.2021.100844. eCollection 2021 May.
BACKGROUND
Surgery is the primary treatment for basal cell carcinoma (BCC). In locally advanced basal cell carcinoma (laBCC), surgery may cause functional or aesthetic damage. In laBCC, neoadjuvant administration of vismodegib, an inhibitor of the Hedgehog signaling pathway, may reduce tumor size, facilitate resection, and reduce functional and aesthetic consequences of surgery. The VISMONEO study assessed efficacy and safety of vismodegib in neoadjuvant treatment of laBCC.
METHODS
VISMONEO (NCT02667574) is an open-label, noncomparative, multicenter, phase 2 study. Patients with ≥1 histologically confirmed facial BCC, inoperable or operable with functional or major aesthetic sequelae risk, were included. Oral vismodegib 150 mg was administered once daily for 4 to 10 months before planned surgery, which was performed once the best response under vismodegib was observed. Primary endpoint was percentage of patients with BCC with tumor downstaging following surgical resection after neoadjuvant vismodegib. Downstaging was defined according to a 6-stage surgical classification related to the aesthetic and functional consequences of surgery.
FINDINGS
55 patients (median age: 73 years) with laBCC were included from November 2014 to June 2015. At inclusion, 4 patients were inoperable, 15 were operable with a major functional risk, and 36 were operable with a minor functional risk or a major aesthetic risk. Mean size of target lesion was 47.3 mm (SD: 27.2 mm). 44 patients presented with downstaging after vismodegib treatment (80%; 95% confidence interval [CI], 67 to 90). Of these 44 patients, 27 had a complete response (25 proved by biopsy). Mean treatment duration was 6.0 months. Overall Response Rate according to RECIST 1.1 criteria was 71% (95% CI, 59 to 88). At 3-years of follow-up, 16/44 patients had known recurrence (36%; 95%CI, 22 to 51).
INTERPRETATION
Neoadjuvant vismodegib allows for a downstaging of the surgical procedure for laBCCs in functionally sensitive locations.
FUNDING
VISMONEO was funded by F. Hoffmann-La Roche Ltd.
背景
手术是基底细胞癌（BCC）的主要治疗方法。在局部晚期基底细胞癌（laBCC）中，手术可能会导致功能或美观方面的损害。在laBCC中，新辅助使用维莫德吉（一种Hedgehog信号通路抑制剂）可能会缩小肿瘤大小，便于切除，并减少手术对功能和美观的影响。VISMONEO研究评估了维莫德吉在laBCC新辅助治疗中的疗效和安全性。
方法
VISMONEO（NCT02667574）是一项开放标签、非对照、多中心的2期研究。纳入了组织学确诊的≥1例面部BCC患者，这些患者不可手术切除或手术切除会有功能或严重美观后遗症风险。在计划手术前4至10个月，每天口服150mg维莫德吉，一旦观察到维莫德吉治疗的最佳反应，即进行手术。主要终点是新辅助使用维莫德吉后手术切除的BCC患者肿瘤降期的百分比。降期根据与手术美观和功能后果相关的6级手术分类来定义。
研究结果
2014年11月至2015年6月纳入了55例laBCC患者（中位年龄：73岁）。纳入时，4例患者不可手术，15例患者手术有严重功能风险，36例患者手术有轻微功能风险或严重美观风险。目标病变的平均大小为47.3mm（标准差：27.2mm）。44例患者在维莫德吉治疗后出现降期（80%；95%置信区间[CI]，67至90）。在这44例患者中，27例有完全缓解（25例经活检证实）。平均治疗持续时间为6.0个月。根据RECIST 1.1标准的总缓解率为71%（95%CI，59至88）。在3年随访时，44例患者中有16例已知复发（36%；95%CI，22至51）。
解读
新辅助使用维莫德吉可使功能敏感部位的laBCC手术降期。
资助
VISMONEO由F. Hoffmann-La Roche Ltd资助。
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