Emerging Nonsurgical Therapies for Locally Advanced and Metastatic Nonmelanoma Skin Cancer

Dermatol Surg. 2019 Jan;45(1):1-16. doi: 10.1097/DSS.0000000000001601.


Background: Locally advanced and metastatic nonmelanoma skin cancer (NMSC) not amenable to surgical resection requires a different approach to therapy.

Objective: To review the efficacy and adverse effects of emerging treatment options for locally advanced and metastatic NMSC.

Materials and methods: A comprehensive search on PubMed was conducted to identify relevant literature investigating the role of program cell death 1 (PD-1) inhibitor, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, epidermal growth factor receptor (EGFR) inhibitor, and Hedgehog pathway inhibitors in the treatment of NMSC.

Results: PD-1 inhibitor and CTLA-4 inhibitor have shown promising efficacy with tolerable side-effect profiles in the treatment of NMSC, although the number of cases reported is limited. Currently, 3 larger-scale clinical trials are investigating PD-1 inhibitor therapy for NMSC. Similarly, EGFR inhibitor demonstrated marginal success in unresectable cutaneous squamous cell carcinomas. Hedgehog pathway inhibitors were approved by the US FDA for treatment of locally advanced and metastatic basal cell carcinomas and have shown favorable efficacy. Common adverse effects included muscle spasm, alopecia, and dysgeusia.

Conclusion: Systemic therapies including PD-1 inhibitors and CTLA-4 inhibitors have demonstrated early promising results for difficult-to-treat NMSC. Future studies are necessary to optimize treatment outcome.

Publication types

  • Review

MeSH terms

  • Anilides / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Biphenyl Compounds / therapeutic use
  • CTLA-4 Antigen / antagonists & inhibitors
  • Carcinoma, Basal Cell / drug therapy*
  • Carcinoma, Basal Cell / secondary
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / therapy*
  • Cetuximab / therapeutic use
  • ErbB Receptors / antagonists & inhibitors
  • Hedgehog Proteins / antagonists & inhibitors*
  • Humans
  • Ipilimumab / therapeutic use
  • Nivolumab / therapeutic use
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Pyridines / therapeutic use
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology


  • Anilides
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Biphenyl Compounds
  • CTLA-4 Antigen
  • Hedgehog Proteins
  • HhAntag691
  • Ipilimumab
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Pyridines
  • sonidegib
  • Nivolumab
  • pembrolizumab
  • ErbB Receptors
  • Cetuximab