Immunomodulators for Non-Melanoma Skin Cancers: Updated Perspectives

Abstract

Non-melanoma skin cancers (NMSCs) are the most common cancers worldwide and may be associated with significant morbidity and mortality, especially in immunosuppressed populations. Successful management of NMSC must take primary, secondary and tertiary prevention strategies into consideration. In response to an improved understanding of the pathophysiology of NMSC and associated risk factors, multiple systemic and topical immunomodulatory drugs have been developed and integrated into clinical practice. Many of these drugs are efficacious in the prevention and treatment of precursor lesions (actinic keratoses; AKs), low-risk NMSC, and advanced disease. The identification of patients at high risk for the development of NMSC is critical in reducing disease morbidity. Understanding the various treatment options available and their comparative effectiveness is paramount for developing a personalized treatment regimen for such patients. This review article provides an updated overview of the various topical and systemic immunomodulatory drugs available for the prevention and treatment of NMSC, and the published data supporting their use in clinical practice.

Keywords:

• non-melanoma skin cancer
• squamous cell carcinoma
• basal cell carcinoma
• keratinocyte carcinoma

Abbreviations

5-FU, 5-fluorouracil; AKs, actinic keratoses; BCC, basal cell carcinoma; BWH, Brigham and Women’s Hospital; CLL, chronic lymphocytic leukemia; COX-2, cyclooxygenase-2; CR, complete response; cSCC, cutaneous squamous cell carcinoma; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; FDA, Food and Drug Administration; HA, hyaluronic acid; HHI, hedgehog inhibitor; IMB, ingenol mebutate; IMI, imiquimod; MAL, methyl aminolevulinate; mTOR, mammalian target of rapamycin; NCCN, National Comprehensive Cancer Network; NMSC, non-melanoma skin cancer; ORR, objective response rate; PD-1, programmed cell death 1 receptor; PD-L1, programmed cell death receptor 1 ligand; PDT, photodynamic therapy; PR, partial response; RCT, randomized-controlled trial; RT, radiation therapy; SOTR, solid organ transplant recipients; UV, ultraviolet.

Disclosure

Kristen Russomanno and Sara Abdel Azim report no conflicts of interest in this work. Vishal Patel discloses honorarium from Sanofi, Regeneron, PhD Biosciences, Biofrontera and Almirall.