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Vismodegib and sonidegib are smoothened (SMO) inhibitors approved for the treatment of advanced basal cell carcinoma (aBCC). This study investigates the real-world experiences and outcomes associated with these therapies across multiple Italian centers. A retrospective, observational, multicenter study was conducted. Medical records of patients with local advanced basal cell carcinoma (laBCC) treated with SMO inhibitors outside of clinical trials from July 2019 to April 2024 were analyzed. A total of 57 patients were included in the study, with 19 (33.3%) receiving vismodegib and 38 (66.7%) receiving sonidegib. Vismodegib demonstrated a complete response (CR) in 31.6% of cases and a partial response (PR) in 26.3%. Sonidegib achieved a CR of 47.4% and a PR of 36.8%. The median treatment duration was 8 months for vismodegib and 12 months for sonidegib. Adverse events were more frequently reported with vismodegib. Treatment interruption due to adverse events occurred in 47.4% of vismodegib recipients and in 13.2% of those receiving sonidegib. The progression of the disease under treatment occurred in 7.9% of cases of patients under sonidegib and in 26.3% of cases under vismodegib. *************************************************************** *Appendix Authors list Valentina Benzecry Mancin,1 Veronica Benzi,2 Matteo Bianco,2,3 Alessandra Bulotta,4 Antonio Costanzo,2,3 Giuseppe Damiano,5 Nerina Denaro,6 Laura Eibenschutz,7 Barbara Merelli,8 Giulia Murgia,1 Alessandra Narcisi,3 Emanuela Passoni,1 Francesco Piscazzi,2,3 Vincenzo Russo5 1Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan; 2Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan; 3Dermatology Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan; 4Department of Oncology, IRCCS San Raffaele, Milan; 5Unit of Immuno-Biotherapy of Melanoma and Solid Tumors, IRCCS Ospedale San Raffaele, Milan; 6Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan; 7Oncologic and Preventive Dermatology Unit, IFO-San Gallicano Dermatological Institute IRCCS, Rome; 8Oncology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy

Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multiple studies demonstrated that the aberrant activation of Hedgehog signaling is a driver of BCC development, and its blockade represents a potential therapeutic target. In Italy, clinicians can prescribe Hedgehog inhibitors (HhIs) Vismodegib and Sonidegib. To highlight the treatment choice of clinicians, we conducted an online survey between November 1 and November 18, 2020 with 33 Italian clinicians from 27 reference hospitals, in which each participant received an anonymous survey consisting of two multiple-choice questions on clinical efficacy and safety profile of Sonidegib and Vismodegib. Respondents reported their opinions on which efficacy and tolerability data of the pivotal phase-II BOLT trial were more relevant in the treatment choice of patients with locally advanced BCC (laBCC). This survey shows that overall response rate (ORR) and the duration of response (DoR) are the most expected across dermatologists and oncologists. The different pharmacokinetic profile of the two HhIs are behind their diverse toxicity spectrum, dose and schedule modification seem to address the choice between vismodegib and sonidegib among dermato-oncology prescribers.

Abstract is missing (Short communication)

Basal cell carcinoma (BCC) is the most commonly diagnosed cutaneous cancer globally. Chronic exposure to environmental triggers and genetic predisposition are risk factors that contribute to the incidence of BCC. While most cases of BCC are treated surgically with curettage or simple excision, treatment options for advanced BCC, including metastatic BCC and locally advanced BCC, are limited as some may be considered unresectable. Advancements in the role of hedgehog signaling in the pathogenesis of BCC have resulted in the development of hedgehog pathway inhibitors as the best treatment for BCC. Germline or somatic mutations in hedgehog pathway signaling components (Smoothened, Patched-1, etc.) result in constant activation of this pathway. Sonidegib and vismodegib are synthetic mimetics of hedgehog pathway inhibitors that are indicated for many subtypes of advanced BCC. We report an unusual case of locally advanced BCC in a 61-year-old male who suffered from a growing BCC for at least six years. After eight months of hedgehog pathway inhibitor (HHI) therapy, the patient reported dramatic improvements in his BCC and complete regression of smaller BCCs previously noted on his upper extremities. The patient reported only minor adverse events including hair thinning, weight loss, and rapidly growing nails., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Koch et al.)