Immune Checkpoint Inhibition in Non-Melanoma Skin Cancer: A Review of Current Evidence.

Connor J Stonesifer,Tiffany J Garcia-Saleem,A Reza Djavid,Yssra S Soliman,Alexandra E Khaleel,Amanda Maisel-Campbell,Richard D Carvajal,Larisa J Geskin,Joseph M Grimes

doi:10.3389/fonc.2021.734354

Abstract

Immuno-oncology is a rapidly evolving field with growing relevance in the treatment of numerous malignancies. The prior study of immunotherapy in dermatologic oncology has largely focused on cutaneous melanoma. However, recent focus has shifted to the use of immunotherapy to treat non-melanoma skin cancers (NMSCs), such as basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC). NMSCs represent the most ubiquitous cancers globally and, while they have a lower propensity to develop into advanced disease than cutaneous melanoma, their absolute mortality burden has recently surpassed that of melanoma. Patients with advanced NMSC are now benefiting from the successes of immunotherapy, including checkpoint inhibition with anti-CTLA-4 and anti-PD-1 monoclonal antibodies. In this review, we discuss the existing clinical evidence for immunotherapy in the treatment of NMSCs, with an emphasis on checkpoint inhibitor therapies. We highlight key studies in the field and provide up-to-date clinical evidence regarding ongoing clinical trials, as well as future study directions. Our review demonstrates that checkpoint inhibitors are positioned to provide unparalleled results in the previously challenging landscape of advanced NMSC treatment.

Highlights

Recent advances in the field of immuno-oncology have translated into breakthrough treatments for many solid and hematological malignancies
non-melanoma skin cancers (NMSCs) represent a significant global health burden that is set to grow ever larger with time, as medical advances permit both a rising average life expectancy and, associatively, an increased risk for NMSC development
Breakthroughs in immunotherapy first touted in the treatment of melanoma have shown promising data in the treatment of advanced NMSCs, where previously few to no effective therapies were available

Summary

INTRODUCTION

Recent advances in the field of immuno-oncology have translated into breakthrough treatments for many solid and hematological malignancies. Immunotherapeutic strategies used in the treatment of melanoma that energize the immune system against these numerous tumor antigens, as in the case of checkpoint inhibitors or oncolytic viral immunotherapies, would be predicted to be effective treatments for NMSCs [7, 12] In some cases, these therapies have demonstrated efficacy and are already being applied in the clinic. In September of 2018, the FDA approved cemiplimab for metastatic and locally advanced cSCC following results from the aforementioned phase 1, open-label, multi-center, dose-finding trial with expansion cohorts (NCT02383212) as well as its follow-up phase 2 study (NCT02760498) (see Figure 4 for a summary of FDA approvals of checkpoint inhibitors for NSMCs). The initial evidence for immune checkpoint inhibition activity in BCC came from limited case reports in the mid-to-late 2010s describing responses in locally advanced and metastatic disease. Mohan et al noted that a patient undergoing treatment with

CONCLUSION

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Results