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

Published Date: 20th September 2026

Publication Authors: Adala. E, Mandal. A, Jones. C

Background
While anti-PD-1 immunotherapy has led to significant improvements in the outcome of advanced cutaneous squamous cell carcinoma (cSCC), over half of patients fail to respond, and there remains no established second-line therapy, representing a clear unmet need.

Aim/Methods
Here, we present a systematic review of the literature and ongoing clinical trials to evaluate current evidence on treatment strategies in this setting. Following a comprehensive search, and quality control assessment of each paper, we identified 20 studies that were included in the final review: 11 published papers, 1 conference poster and 8 ongoing clinical trials. Data from the 12 reported studies were presented in a study-by-study format. Outcomes were reported descriptively and included the overall response rate (ORR), complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD), progression-free survival (PFS) and, where available, overall survival (OS).

Results
Although the review is limited by small sample sizes and the frequent use of combination rather than monotherapy regimens, the evidence suggests that epidermal growth factor receptor (EGFR) inhibitor-containing treatment strategies are the most frequently reported salvage approach and demonstrate preliminary evidence of treatment activity in advanced cSCC following anti-PD-1 failure.

Conclusions
However, current evidence is insufficient to establish superiority over alternative treatments. Other treatment strategies, such as ipilimumab, oncolytic virotherapy and chemo-immunotherapy, show clinical promise warranting further investigation.

Thomson. H; Adala, E; Mandal, A; Jones, C; Sacco, JJ. (2026). Treatment Strategies for Advanced Cutaneous Squamous Cell Carcinoma Following Anti-PD-1 Immunotherapy Failure: A Systematic Review of the Literature and Ongoing Trials. Cancers. 18(18), p.3060. [Online]. Available at: https://doi.org/10.3390/cancers18183060 [Accessed 1 October 2026]