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.
© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.