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

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.

Changing trends in the disease burden of non-melanoma skin cancer globally from 1990 to 2019 and its predicted level in 25 years

“…Ferlay shows that worldwide estimated mortality rates for all types of NMSC were higher than the corresponding mortality rates for melanoma, mesothelioma, oropharyngeal, and thyroid cancers [ 29 ]. NMSC causes a substantial economic burden worldwide [ 30 , 31 ]. It was the most expensive cancer in Australia, with an expenditure of $511 million in 2010 [ 32 ].…”

Skin Cancer Research Goes Digital: Looking for Biomarkers within the Droplets

“…Outcomes are generally inferior with RT without surgical resection and tumors may recur quickly after the treatment [ 119 , 120 ]. Novel systemic approaches, such as targeted therapies and immunotherapies, have revolutionized skin cancer therapy and improved clinical care, especially in the metastatic setting [ 118 , 121 ]. Hedgehog pathway inhibitors (HHi), vismodegib and sonidegib, are relevant examples in this context.…”

PET-CT in Clinical Adult Oncology—VI. Primary Cutaneous Cancer, Sarcomas and Neuroendocrine Tumors

“…Many advanced cutaneous malignancies now employ immunotherapy, typically with checkpoint inhibitors, for metastatic disease or for adjuvant control in higher risk patients [ 5 , 6 , 7 , 8 ]. These are often used in combination or in conjunction with chemotherapy or other types of targeted therapies, such as anti-programmed cell death protein (PD)-1 antibodies or mitogen-activated protein kinase enzymes (MEKs) and BRAF inhibitors.…”