PMID- 37311439 OWN - NLM STAT- MEDLINE DCOM- 20231207 LR - 20231207 IS - 1421-9832 (Electronic) IS - 1018-8665 (Linking) VI - 239 IP - 6 DP - 2023 TI - Clinical Characteristics of an Italian Patient Population with Advanced BCC and Real-Life Evaluation of Hedgehog Pathway Inhibitor Safety and Effectiveness. PG - 868-876 LID - 10.1159/000531280 [doi] AB - 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 (HHIs) changed the treatment landscape for this complex patient population. OBJECTIVES: The aims of the present study are 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 [laBCC] and metastatic BCC [mBCC]) 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 were available for 132 (74.1%) of 178 patients: 129 patients had a diagnosis of laBCC (n = 84, sonidegib; n = 45, vismodegib) and 3 patients of mBCC (n = 2, vismodegib; n = 1, sonidegib, off-label). Objective response rate was 76.7% (95% confidence interval [CI]: 82.3-68.7) and 33.3% (95% CI: 88.2-1.7) for laBCC (complete response [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 nonresponse 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. CI - (c) 2023 S. Karger AG, Basel. FAU - Mannino, Maria AU - Mannino M AD - UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endrocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy, mariamannino04@yahoo.it. AD - Dermatologia, Universita Cattolica del Sacro Cuore, Rome, Italy, mariamannino04@yahoo.it. FAU - Piccerillo, Alfredo AU - Piccerillo A AD - Dermatologia, Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Fabbrocini, Gabriella AU - Fabbrocini G AD - Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy. FAU - Quaglino, Pietro AU - Quaglino P AD - Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy. FAU - Argenziano, Giuseppe AU - Argenziano G AD - Dermatology Unit, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Dika, Emi AU - Dika E AD - Dermatology - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. AD - Department of Experimental, Diagnostic and Specialty Medicine (DIMES) Alma Mater Studiorum University of Bologna, Bologna, Italy. FAU - Ascierto, Paolo Antonio AU - Ascierto PA AD - Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Pascale, Naples, Italy. FAU - Pellacani, Giovanni AU - Pellacani G AD - Department of Dermatology, University of Rome La Sapienza, Rome, Italy. FAU - Longo, Caterina AU - Longo C AD - Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy. AD - Azienda Sanitaria Locale, IRCCS di Reggio Emilia, Centro Oncologico ad Alta Tecnologia Diagnostica-Dermatologia, Reggio Emilia, Italy. FAU - Fargnoli, Maria Concetta AU - Fargnoli MC AD - Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. FAU - Bianchi, Luca AU - Bianchi L AD - Dermatology Unit, Tor Vergata University Hospital, Rome, Italy. FAU - Calzavara-Pinton, Piergiacomo AU - Calzavara-Pinton P AD - Department of Dermatology, ASST-Spedali Civili, University of Brescia, Brescia, Italy. FAU - Zalaudek, Iris AU - Zalaudek I AD - Department of Dermatology, University of Trieste, Trieste, Italy. FAU - Fava, Paolo AU - Fava P AD - Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy. FAU - Scalvenzi, Massimiliano AU - Scalvenzi M AD - Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy. FAU - Bocchino, Enrico AU - Bocchino E AD - UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endrocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy. AD - Dermatologia, Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Di Stefani, Alessandro AU - Di Stefani A AD - UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endrocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy. AD - Dermatologia, Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Peris, Ketty AU - Peris K AD - UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endrocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy. AD - Dermatologia, Universita Cattolica del Sacro Cuore, Rome, Italy. CN - and Collaborators LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20230613 PL - Switzerland TA - Dermatology JT - Dermatology (Basel, Switzerland) JID - 9203244 RN - 0RLU3VTK5M (sonidegib) RN - 0 (HhAntag691) RN - 0 (Hedgehog Proteins) RN - 0 (Anilides) RN - 0 (Antineoplastic Agents) SB - IM MH - Humans MH - Adolescent MH - Adult MH - *Skin Neoplasms/pathology MH - Hedgehog Proteins/metabolism/therapeutic use MH - Reproducibility of Results MH - *Carcinoma, Basal Cell/drug therapy/pathology MH - Anilides/adverse effects MH - *Antineoplastic Agents/adverse effects OTO - NOTNLM OT - Advanced BCC OT - Nonmelanoma skin cancer OT - Real-life data OT - Sonidegib OT - Vismodegib EDAT- 2023/06/14 01:10 MHDA- 2023/12/07 12:42 CRDT- 2023/06/13 18:23 PHST- 2023/03/01 00:00 [received] PHST- 2023/05/22 00:00 [accepted] PHST- 2023/12/07 12:42 [medline] PHST- 2023/06/14 01:10 [pubmed] PHST- 2023/06/13 18:23 [entrez] AID - 000531280 [pii] AID - 10.1159/000531280 [doi] PST - ppublish SO - Dermatology. 2023;239(6):868-876. doi: 10.1159/000531280. Epub 2023 Jun 13.