title: Defining locally advanced basal cell carcinoma and integrating smoothened inhibitors into clinical practice.
abstract: OBJECTIVE
  We summarize the concept of a locally advanced basal cell carcinoma (laBCC) and present the current consensus definition. We also review the key pieces of primary research undertaken in the past year and how these affect the use of smoothened inhibitors in a clinical setting.
  
  
  RESULTS
  Medium term follow-up (30 months) of patients treated with vismodegib shows an improvement in response rates for patients with laBCC. The safety profile of vismodegib demonstrated in the original ERIVANCE study has been replicated in a larger patient cohort in a repeat study. Sonidegib is a new smoothened inhibitor currently under investigation for treatment of laBCC, which demonstrates a comparable safety profile to vismodegib. The side-effects of smoothened inhibitors appear related to both dose and duration of treatment. The durability of response to vismodegib is uncertain, but has been observed to last for over a year following discontinuation of treatment.
  
  
  CONCLUSIONS
  The understanding of the efficacy and safety of vismodegib has improved since its introduction in 2012. A broadening evidence base supports its use as a valid treatment for laBCC. However, questions remain as to how to integrate its use into existing pathways for treating laBCC and its long-term efficacy.
authors.affiliation: aNorfolk and Norwich University Hospital NHS Foundation Trust, Norwich bSt John's Institute of Dermatology, St Thomas' Hospital, London cSalford Royal NHS Foundation Trust, University of Manchester, Manchester, UK.
authors.forename: Andre B S
authors.initials: AB
authors.lastname: Khoo
authors.forename: Faisal R
authors.initials: FR
authors.lastname: Ali
authors.forename: John T
authors.initials: JT
authors.lastname: Lear
mesh_terms: D000813:Anilides / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000175:diagnosis / Q000188:drug therapy*; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D011725:Pyridines / Q000627:therapeutic use*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D012878:Skin Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D000072086:Smoothened Receptor
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D053823:Hedgehog Proteins; C538724:HhAntag691; D011725:Pyridines; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; C561435:sonidegib