Using drug scheduling to manage adverse events associated with hedgehog pathway inhibitors for basal cell carcinoma

// John T. Lear 1 , Reinhard Dummer 2 , 3 and Alexander Guminski 4 , 5 1 Manchester Academic Health Science Centre, University of Manchester, Manchester, UK 2 Department of Dermatology, University Hospital, University of Zurich, Zurich, Switzerland 3 Skin Cancer Center, University Hospital, University of Zurich, Zurich, Switzerland 4 Department of Medical Oncology, Royal North Shore Hospital, St Leonards, Australia 5 Faculty of Medicine, Sydney Medical School, The University of Sydney, Sydney, Australia Correspondence to: John T. Lear, email: john.lear@srft.nhs.uk Keywords: adverse events; basal cell carcinoma; sonidegib; hedgehog inhibitor; drug scheduling Received: October 08, 2021 Accepted: November 10, 2021 Published: December 21, 2021 Copyright: © 2021 Lear et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Basal cell carcinoma (BCC) is the most common malignancy and form of skin cancer worldwide; advanced BCC, either as locally advanced BCC (laBCC) or metastatic BCC (mBCC), can cause substantial tissue invasion and morbidity. Until the recent availability of the hedgehog pathway inhibitors (HHIs) sonidegib and vismodegib, treatment options for advanced BCC were limited. These agents demonstrate efficacy in patients with laBCC and mBCC; however, the adverse events (AEs) associated with these agents can lead to treatment interruption or discontinuation and reduced quality of life, all of which significantly impact long-term adherence to therapy, which might affect clinical outcome. Given that most AEs are class-related effects, switching HHIs does not appear to lead to a significantly different AE profile, underscoring the importance of maintaining patients on their first HHI. Interrupting treatment of sonidegib and vismodegib does not appear to undermine the efficacy of these agents and is therefore a practical option to manage AEs in order to maintain continued treatment and disease control.