Systemic therapy for locally advanced and metastatic non-melanoma skin cancer

Non-melanoma skin cancer (NMSC) is the most common form of cancer diagnosed in the United States, affecting 3.3 million individuals with a total of 5.4 million NMSCs diagnosed in the United States annually (Rogers et al., JAMA Dermatol. 06360:1081-1086, 2015). NMSC is typically considered a localized neoplasm with variable metastatic potential (0.0028-0.55% for basal cell carcinoma (BCC) and 5.2% for primary cutaneous squamous cell carcinoma (cSCC)) (Lo et al., J Am Acad Dermatol. 24(5 Pt 1):715-9, 1991; Seo et al., Ann Dermatol. 23(2):213-6, 2011; Kauvar et al. Dermatol Surg. 41(11):1214-40, 2015). In general, the standard treatment modality for NMSC has been surgical excision; nevertheless, those patients with inoperable tumors or metastatic disease necessitate a different treatment approach. Considering that approximately 30% of patients with unresectable cSCC responded to treatment of any kind, and the overall survival for these individuals is less than a year, recent advances in research have been driven by the unmet need of patients with advanced NMSC disease (Jarkowski et al. Am J Clin Oncol. 00(00):1-4, 2014; Gatalica et al. Cancer Epidemiol Biomark Prev. 23(12):2965-70). This chapter focuses on the discussion of systemic therapeutic options with hedgehog pathway inhibitors and immunotherapy.