Immune Checkpoint Inhibitors for Advanced Cutaneous Squamous Cell Carcinoma: A Systematic Review with Meta-Analysis

Background Results of early trials led to FDA approval of immune checkpoint inhibitors (ICIs) for advanced and recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (CSCC). Updated data from these trials are pending and extent of survival outcomes is undetermined. Objective The aim of this study was to assess the efficacy of ICIs in advanced CSCC, comprising locally advanced (LA), locoregionally advanced (LR), and recurrent or metastatic (R/M) disease. Patients and Methods A systematic review of four databases (PubMed, Scopus, OVID, Cochrane) and meta-analysis of proportions was performed. Phase I and II prospective clinical trials were included. Results Six trials evaluating cemiplimab ( n = 3) and pembrolizumab ( n = 3) were eligible for inclusion. Overall survival (OS) was not reached at data-cutoff. Pooled analysis of 392 patients demonstrated that ICIs conferred an objective response rate (ORR) of 42.43% (95% CI 37.53–47.45) and disease control rate (DCR) of 58.05% (95% CI 53.04–62.95). Patients with LR or distant metastatic lesions achieved equivalent ORRs and DCRs. Duration of response (DOR) was not reached in all trials and 92% of all responders continued to have therapeutic response at data cut-off. Tolerability was favorable, with only 27.12% (95% CI 10.89–47.38) of patients experiencing grade ≥ 3 adverse events. Conclusion Surgical treatment of CSCC remains the guideline-based standard of care for curative intent of local, LA, and LR disease. ICIs demonstrate promising results for LA, LR, and R/M CSCC not amenable to surgery. Endpoints assessing survival and durability of response have not been reached, warranting additional trials exploring neoadjuvant or adjuvant therapy in combination with local treatment.