A Review of the Risk of Cutaneous Squamous Cell Carcinoma after Vismodegib Therapy

Abstract

Since vismodegib’s approval for advanced or metastatic basal cell carcinoma, there has been concern over vismodegib’s potential to induce secondary neoplasms of the skin, such as cutaneous squamous cell carcinoma (cSCC). In this article, we provide a comprehensive review of the literature on vismodegib’s relationship to cSCC. A systematic search of PubMed and Ovid MEDLINE was performed with terms “vismodegib” AND “squamous cell carcinoma.” Studies ranged from May 2013 to January 2022 and 25 articles were ultimately included. In total, of the 2576 patients included in the review, there were 197 cSCCs reported. Numerous reports have published conflicting findings. While one retrospective cohort study did find an increased risk, additional studies have found that the rates of cSCC are comparable between those exposed and those not exposed. Because a causal relationship between vismodegib and cSCC has not been proven, its use should not be avoided due to concerns of causing cSCC. However, patients treated with vismodegib should be closely monitored by dermatologists to evaluate for any suspicious changes. Large-scale, prospective, multi-center studies should be performed to definitively determine the risk of cSCC and vismodegib. It has been proposed that vismodegib may select for tumor cells utilizing the Ras/MAPK pathways.