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.

Management of Locally Advanced Basal Cell Carcinoma with Sonic Hedgehog Pathway Targeted Therapy: A Case Report and Discussion

“…The development of a synchronous SCC during vismodegib therapy is consistent with the previously described increased risk of developing a non-BCC malignancy while undergoing systemic hedgehog inhibitor therapy [ 20 ]. Although a causal relationship has not been proven, increasing evidence suggests an association [ 21 , 22 ]. Our case report supports the current recommendation that patients treated with hedgehog pathway inhibitors need close surveillance to assess and biopsy any new concerning lesions.…”

Cutaneous Squamous Cell Carcinoma: An Updated Review

“…Vismodegib, a hedgehog pathway inhibitor indicated for advanced or metastatic basal cell carcinoma (BCC), was previously shown to have an 8-fold increase of cSCC, but this conclusion has not been reproducible in recent studies [42,43]. Thus, more research is warranted.…”