Vismodegib and Sonidegib Are Associated With an Elevated Reporting Odds of Squamous Cell Carcinoma; a Comparative Pharmacovigilance Study of the FDA Adverse Events Reporting System ( FAERS )

BACKGROUND: Direct comparison of the adverse effect (AE) profiles of the hedgehog inhibitor (HIs) medications is limited to post hoc analyses of phase III clinical trials. OBJECTIVE: Compare the AE profiles between vismodegib and sonidegib in the FDA Adverse Event Reporting System (FAERS). METHODS: Case/non-case analyses were performed in FAERS and reporting odds ratios (ROR) were compared to determine unique and disproportionate AEs between HIs. RESULTS: Vismodegib had significantly higher ROR for taste symptoms and alopecia. Sonidegib was associated with neutropenia and elevated blood creatinine phosphokinase. Both vismodegib and sonidegib were associated with an increased ROR for cSCC (50.36 [42.36-59.86] vs. 50.28 [27.71-91.23]). This signal persisted despite comparison to an aggregate of other medications used to treat basal cell carcinoma (BCC) (11.56 [9.51-14.05] vs. 9.71 [1.25-75.43]). LIMITATIONS: Retrospective nature predisposed to bias. CONCLUSIONS: Vismodegib has a significantly higher ROR for alopecia and taste symptoms, while sonidegib was associated with neutropenia, which is a novel finding. Both HIs are associated with an increased ROR for cSCC, which persists despite stringent controls and does not parallel total cSCC cases reported to FAERS. These data suggest that HIs increase the risk of cSCC above the baseline expected in this patient population.