Immunotherapy and Its Timing in Advanced Basal Cell Carcinoma Treatment

For patients with advanced basal cell carcinoma (BCC), including locally advanced or metastatic BCC not amenable to curative surgery or radiotherapy, hedgehog pathway inhibitors (HHI) vismodegib and sonidegib are approved as first-line systemic treatment. Results from clinical trials highlight that the overall discontinuation rate of HHI treatment varies from 88% to 92% with vismodegib and is approximately 92% with sonidegib, and half of patients will discontinue HHI after approximately 8 to 12 months. The main factors weighing in on the decision to discontinue HHI include efficacy (tumor response), adverse events and patient decision. In clinical practice, some of the patients that stop HHI may be re-evaluated if the tumor becomes amenable to surgery, or restart HHI at a later time, while others will need to switch to immunotherapy, depending on the reasons for HHI discontinuation. In this review, we revisit the therapeutic decisions considering a switch from HHI to immunotherapy with anti-PD-1 agent cemiplimab and we highlight the place of cemiplimab in the therapeutic ladder for patients with advanced BCC. We discuss the evidence on the efficacy and safety of anti-PD-1 agents as second-line systemic monotherapy, or in combination with other treatments, and the emergence of checkpoint immunotherapy as a neoadjuvant treatment.