Treatment Strategies for Advanced Cutaneous Squamous Cell Carcinoma Following Anti-PD-1 Immunotherapy Failure: A Systematic Review of the Literature and Ongoing Trials

Abstract

Simple Summary Cutaneous squamous cell carcinoma is a common type of skin cancer that is usually cured with surgery. However, some patients develop advanced disease that cannot be removed surgically or spreads to other parts of the body. Although immunotherapy has improved outcomes, many patients do not respond to treatment or their cancer progresses, and there is currently no clear evidence to guide the next stage of treatment. This systematic review brings together the available research on treatments used after immunotherapy failure and examines ongoing clinical trials investigating new approaches. The findings suggest that epidermal growth factor receptor-containing strategies are the most frequently reported salvage approach and demonstrate preliminary evidence of treatment activity. However, the available evidence is limited by small, heterogeneous, non-randomised cohorts and is insufficient to establish superiority over alternative treatments. Several other promising immunotherapy-based strategies are also under investigation. This review provides an up-to-date summary of the available evidence to support clinical decision-making and help guide future research in this challenging area.