33 | A single center, real world experience with hedgehog pathway inhibitors in advanced basal cell carcinoma

Giulia Gibilisco¹, Ramiz Anwar Rana¹, Vincenzo D’Alonzo¹, Maura Colucci^1|2, Monica Valente², Elisa Cinotti³, Giovanni Rubino⁴, Valentina Croce¹, Eleonora Carbonari¹, Matteo Ravara¹, Tommaso Sani¹, Maria Lo Fiego¹, Alessia Covre¹, Serena Cutarella¹, Roberto Cuomo⁵, Luca Grimaldi⁵, Pietro Rubegni³, Michele Maio^1|2, Anna Maria Di Giacomo^1|2 | ¹University of Siena; ²Center for Immuno-Oncology, Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena; ³Dermatology Unit, Department of Medicine, Surgery and Neuroscience, University Hospital of Siena; ⁴Radiotherapy Unit, Department of Oncology, University Hospital of Siena; ⁵Plastic Surgery Unit, Department of Medicine, Surgery and Neuroscience, University Hospital of Siena; ⁶NIBIT Foundation Onlus, Genoa, Italy.

Background: Cutaneous basal cell carcinoma (cBCC) is the most common non melanocytic skin cancer, with a worldwide increased incidence. Basal cell carcinomas are heterogeneous, ranging from superficial or nodular lesions with a good prognosis to extensive, difficult-to-treat lesions requiring a multidisciplinary approach. The Hedgehog pathway inhibitors (HHIs), sonidegib and vismodegib, have received regulatory approval for the treatment of advanced BCC (aBCC) due to their impressive clinical efficacy in multicenter phase 2 clinical trials with an ORR of 56% [95% CI: 43-68] 1 and 43% [95% CI: 31-56] 2 respectively. Based on these remarkable results, HHIs are currently the standard of care for aBCC patients and real-world data can help the daily practice.

Methods: This real-world experience included adult patients with aBCC treated with HHIs at the Center for Immuno-Oncology, University Hospital of Siena, Italy. Clinical outcome and adverse events (AEs) are reported.

Results: Between January 2016 and November 2024, 33 patients (21 male; median age 73 years [range 32-90]) diagnosed with aBCC were treated with HHIs (28 sonidegib, 5 vismodegib). The most common primary tumor location was head and neck (63.6%), followed by trunk (18.2%), lower extremities (15.2%) and upper extremities (3%). Three patients (9.1%) had undergone radiotherapy, before HHI treatment. As of June 2025, with a median follow-up of 34.7 months (range 4–126), the ORR was 45.5% (CR 18.2%) with a DCR of 97.0%. Median progression free survival (mPFS) was 61 months [95% CI: 56-72], and median overall survival (mOS) was 92 months [95% CI: 64-95]. The 1-year PFS and OS rates were 94% [95% CI: 86-100] and 94% [95% CI: 86-100] while the 2-year rates were 77% [95% CI: 64-94] and 87% [95% CI: 76-100], respectively. Treatment was well tolerated with 3 (9.1%) patients experiencing grade ≥ 3 treatment-related adverse events (TRAEs), The most severe TRAE was rhabdomyolysis (grade 4) followed by atrial fibrillation (grade 3) and hypocalcemia (grade 3). Treatment was discontinued in 4 patients (12.1%) due to TRAEs.

Conclusions: Our real-world experience in patients with aBCC confirms the high response rate and the good tolerability of HHIs.

References:
[1] Dummer R, Guminksi A, Gutzmer R, et al. Long-term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase II randomized, double-blind BOLT study. Br J Dermatol. 2020;182(6):1369-1378.
[2] Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366(23):2171-2179.