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

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Abstract

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.

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA

    Neil K. Mehta, Andraia R. Li, Shaun A. Nguyen, David M. Neskey & Terry A. Day

  2. Department of Medicine, Hematology and Oncology, Medical University of South Carolina, Charleston, SC, USA

    John M. Kaczmar

  3. Hollings Cancer Center, Charleston, SC, USA

    John M. Kaczmar, David M. Neskey & Terry A. Day

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  1. Neil K. Mehta
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Correspondence to Neil K. Mehta.

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No external funding was used in the preparation of this manuscript.

Conflicts of interest

Neil K. Mehta, Andraia R. Li, Shaun A. Nguyen, John M. Kaczmar, David M. Neskey, and Terry A. Day declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Author’s contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by NKM, ARL, TAD, SAN, JMK. The first draft of the manuscript was written by Neil K. Mehta. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Mehta, N.K., Li, A.R., Nguyen, S.A. et al. Immune Checkpoint Inhibitors for Advanced Cutaneous Squamous Cell Carcinoma: A Systematic Review with Meta-Analysis. Targ Oncol 16, 743–752 (2021). https://doi.org/10.1007/s11523-021-00844-z

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