Supplementary Material for: Predictive Factors of Non-Response to Vismodegib in Locally Advanced Basal-Cell Carcinoma

Background: Vismodegib has shown clinical efficacy in the management of locally advanced basal cell carcinomas (laBCC). However, non-response to vismodegib is observed in 2–13.5% of patients in clinical studies. The purpose of this study was to identify factors associated with non-response to vismodegib in patients with laBCC. Methods: We carried out a retrospective multicenter study, including patients with laBCC treated with vismodegib, from July 2011 to May 2019. Response to treatment was assessed according to the RECIST 1.1 criteria. Patients were categorized as responders with a complete response or a partial response or non-responders with a stable disease or a progressive disease according to what has been observed during follow-up. Patient demographics, tumor profile, and treatment modalities were compared in responders and non-responders. Results: Eighty-three patients with laBCC were included in the study. Twenty-five (30.1%) were non-responders to vismodegib. History of treatment with radiotherapy, presence of muscle involvement and intermittent treatment with vismodegib were significantly associated with a non-response (p p = 0.025, p p = 0.2) and morpheaform IaBCC subtype (p = 0.056) were more frequent in non-responders without reaching statistical significance. Conclusion: In this study, non-response of laBCC to vismodegib therapy was associated with muscle involvement. Previous radiotherapy and intermittent use of vismodegib have been identified as causes favoring non-response to vismodegib. Due to the low numbers of patients included in the study, it is difficult to draw firm conclusions. Further studies are needed to confirm these data.研究背景：维莫德吉（Vismodegib）在局部晚期基底细胞癌（laBCC）的诊疗管理中已展现出临床疗效。然而，临床研究显示2%~13.5%的患者会出现维莫德吉治疗无应答的情况。本研究旨在明确局部晚期基底细胞癌（laBCC）患者接受维莫德吉治疗后出现无应答的相关影响因素。 研究方法：本研究为回顾性多中心研究，纳入2011年7月至2019年5月期间接受维莫德吉治疗的局部晚期基底细胞癌患者。依据实体瘤疗效评价标准1.1版（RECIST 1.1）评估患者的治疗应答情况；根据随访期间的观察结果，将患者分为应答者（完全应答或部分应答）与无应答者（疾病稳定或疾病进展）两类。对比应答者与无应答者的人口统计学特征、肿瘤特征及治疗方案。 研究结果：本研究共纳入83例局部晚期基底细胞癌患者，其中25例（30.1%）对维莫德吉治疗无应答。既往放疗史、肌肉受累及维莫德吉间歇性给药与治疗无应答显著相关（原文本存在重复p值标注：p=0.025、p=0.2）；硬化型laBCC亚型在无应答者中占比更高，但未达到统计学显著性差异（p=0.056）。 研究结论：本研究显示，局部晚期基底细胞癌患者对维莫德吉治疗无应答与肌肉受累相关。既往放疗史与维莫德吉间歇性给药被证实为导致治疗无应答的危险因素。由于本研究纳入的患者例数较少，尚难以得出确定性结论，需开展进一步研究以验证本研究结果。