Integration of immunotherapy and radiotherapy in a therapeutic algorithm for locally advanced squamous cell skin cancer.

Locally advanced squamous cell skin cancer (LA-sqCSC) affects older patients who initially decline medical assistance and patients after multiple surgical interventions for recurrent tumors. Radical radiotherapy (RT) often becomes difficult to apply due to large surface areas, extensive ulceration, and tissue necrosis. Thirty patients with LA-sqCSC were treated according to a therapeutic algorithm involving upfront immunotherapy (IO) with cemiplimab (anti-PD-1 MoAb) and RT. Patients with progressive or stable disease (PgD, SD) or partial/minimal response (PR/MR) received local RT (6 daily fractions of 6 Gy) concurrently with cemiplimab. Complete responders (CR) after IO continued cemiplimab, till progression or development of immune-related adverse events (irAEs) for a maximum of 18 months. irAEs enforced interruption of cemiplimab in 6/30 (20.0%) patients. After the 6th cycle of IO, the CR rates were 50.0%. Nine patients with PR/MR to IO underwent RT. Six of them (66.7%) responded completely. The overall CR rates of patients treated with the proposed algorithm were 70.0%. The 2-year projected locoregional progression-free survival was 68.4% and the disease-specific overall survival was 85.2%. LA-sqCSC can be effectively treated with upfront cemiplimab IO followed by a short course of hypofractionated RT directed to the residual tumor.