Risk of cutaneous squamous cell carcinoma after treatment of basal cell carcinoma with vismodegib

Background: Vismodegib is a first-in-class agent targeting the hedgehog signaling pathway for treatment of patients with locally advanced basal cell carcinoma (BCC) and metastatic BCC. There have been concerns about the development of squamous cell carcinoma (SCC) in patients treated with this drug. Objective: We sought to determine whether treatment with vismodegib is associated with an increase in the risk of cutaneous SCC. Methods: In this retrospective cohort study, patients treated with vismodegib as part of phase I and II clinical studies were compared with participants from the University of California, San Francisco, Nonmelanoma Skin Cancer Cohort who received standard therapy for primary BCC. In total, 1675 patients were included in the analysis, and the development of SCC after vismodegib exposure was assessed. Results: The use of vismodegib was not associated with an increased risk of subsequent development of SCC (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28-1.16). Covariates including age, sex, history of previous nonmelanoma skin cancer, and number of visits per year were significantly associated with the development of SCC. Limitations: A limitation of the study was that a historic control cohort was used as a comparator. Conclusions: Vismodegib was not associated with an increased risk of subsequent SCC when compared with standard surgical treatment of BCC.