Long-term strategies for management of advanced basal cell carcinoma with hedgehog inhibitors
Paolo Bossi, Paolo A. Ascierto, Nicole Basset‐Séguin, Brigitte Dréno, Reinhard Dummer, Axel Hauschild, Peter Mohr, Roland Kaufmann, Giovanni Pellacani, Susana Puig, D. Moreno‐Ramírez, Caroline Robert, Alex Stratigos, Ralf Gutzmer, Paola Queirolo, Pietro Quaglino, Ketty Peris
Abstract
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. • Aberrant activation of the hedgehog molecular pathway plays a pivotal role in the pathogenesis of basal cell carcinoma. • Systemic therapy is indicated when surgery and radiotherapy are inappropriate or contraindicated. • The hedgehog inhibitors are first-line systemic treatments for advanced BCC, achieving an early and long-lasting response. • Long-term treatment is challenged by tolerability issues but several strategies are currently available to manage them. • Experts recommend immunotherapy in patients with resistance to hedgehog inhibitors or persistence toxicity despite long-term management of AE.