Clinical Characteristics of an Italian Patient Population with Advanced BCC and Real-Life Evaluation of Hedgehog Pathway Inhibitor Safety and Effectiveness

Background: Advanced basal cell carcinoma (aBCC) represents a complex and clinically heterogeneous group of lesions for which curative surgery and/or radiotherapy is unlikely. Systemic therapy with hedgehog pathway inhibitors (HHI) changed the treatment landscape for this complex patient population.Objectives: to describe the clinical characteristics of a real-life Italian cohort diagnosed with aBCC, and to investigate effectiveness and safety of HHI.Methods: a multicenter observational study was performed by twelve Italian centers in the period January 1, 2016 - October 15, 2022. Patients aged >= 18 years and diagnosed with aBCC (locally advanced and metastatic BCC) were eligible for the study. Methods for investigating tumor response to HHI included clinical and dermatoscopic evaluation, radiological imaging, and histopathology. For HHI safety assessment, therapy-related adverse events (AEs) were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.Results: we enrolled 178 patients under treatment with HHI: 126 (70.8%) and 52 patients (29.2%) received sonidegib and vismodegib, respectively. Comprehensive data on HHI effectiveness and disease outcome was available for 132 (74.1%) of 178 patients: 129 patients had a diagnosis of locally advanced BCC (laBCC) (n=84, sonidegib; n=45, vismodegib), and 3 patients of metastatic BCC (mBCC) (n=2, vismodegib; n=1, sonidegib, off-label). Objective response rate (ORR) was 76.7% (95% CI: 82.3-68.7) and 33.3% (95% CI: 88.2-1.7) for laBCC (CR: 43/129; PR: 56/129) and mBCC (CR: 0/3; PR: 1/3), respectively. High-risk aBCC histopathological subtypes and occurrence of >2 therapy-related AEs were significantly associated with non-response to HHI therapy [(OR: 2.61; 95% CI: 1.09-6.05; p:0.03) and (OR: 2.74; 95% CI: 1.03-7.9; p:0.04)], respectively. Majority of our cohort (54.5%) developed at least 1 therapy-related AE, most of which were mild-moderate in severity.Conclusions: our results demonstrate the effectiveness and safety profile of HHI and confirm the reproducibility of pivotal trial results in real-life clinical setting.