Long-term strategies for management of advanced basal cell carcinoma with hedgehog inhibitors.

Basal cell carcinoma (BCC), the most common type of skin cancer, is characterized by aberrant activation of the hedgehog molecular pathway. Systemic therapy is indicated when local approaches, such as surgery and radiation, are inappropriate. In this article, a group of clinical experts recommends the long-term management strategy for advanced BCC patients treated with systemic therapy. The hedgehog inhibitors sonidegib and vismodegib are first-line treatments for advanced BCC with a long-lasting response, but long-term treatment with hedgehog inhibitors is often challenged by tolerability issues. However, several strategies for adverse effect management are available, such as dose interruptions, on-label alternate-day dosing and supportive medications. In conclusion, although BCC shows a high tumor mutational burden that favors a response to immunotherapy, experts recommend keeping patients on hedgehog inhibitors limiting immunotherapy to those who developed resistance during hedgehog inhibitor therapy or in case of persisting toxicity despite long-term management of adverse events.

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Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following conflicts of interest. Pietro Quaglino: advisory boards and speaker fees from Sanofi, SUNPharma, Roche. Ralf Gutzmer: research support to Pfizer, Johnson&Johnson, Novartis, Amgen, Sanofi, Merck-Serono, Kyowa-Kirin, Almirall; honoraria for lectures from Roche Pharma, Bristol-MyersSquibb, Novartis, MSD, Almirall-Hermal, Amgen, Merck-Serono, Bayer, SUN, Pierre-Fabre, Sanofi; honoraria for advice from Roche Pharma, Bristol-MyersSquibb, Novartis, MSD, Almirall-Hermal, Amgen, Pierre-Fabre, Merck-Serono, 4SC, SUN, Sanofi, Immunocore; support for participation in meetings from Roche Pharma, Bristol-MyersSquibb, Pierre-Fabre, Merck-Serono, SUN, Merck-Serono. Brigitte Dreno: personal fees for board meetings from Roche, Regeneron and Sun Pharma. Paolo Ascierto: consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health, ValoTX. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi. Roland Kaufmann: institutional grants outside the submitted talk and entirely linked to clinical trials from Novartis and Roche, and grants from AbbVie, Amgen, Astra Zeneca, Biontech, BMS, Celgene, Galderma, Incyte, Janssen, Leo, Lilly.