An investigator-initiated open-label clinical trial of vismodegib as a neoadjuvant to surgery for high-risk basal cell carcinoma

J Am Acad Dermatol. 2014 Nov;71(5):904-911.e1. doi: 10.1016/j.jaad.2014.05.020. Epub 2014 Jun 11.

Abstract

Background: Vismodegib is an oral hedgehog-pathway inhibitor approved for advanced basal cell carcinoma (BCC). Although most BCCs are amenable to surgery, excision of large tumors in aesthetically sensitive sites may compromise function or cosmesis.

Objective: We sought to evaluate the reduction in BCC surgical defect area after 3 to 6 months of neoadjuvant vismodegib.

Methods: This was an open-label, single-arm intervention trial with a primary outcome of change in target-tumor surgical defect area pre- and post-vismodegib (150 mg/d). Secondary outcomes were change in tumor area and tolerability.

Results: Eleven of 15 enrolled patients, aged 39 to 100 years, completed the trial. Thirteen target tumors were excised after a mean of 4±2 months of vismodegib. In all, 29% (4 of 14 patients) could not complete more than 3 months because of vismodegib-related side effects. The mean baseline target-tumor diameter was 3.2 cm, and 10 of 13 tumors occurred on the face. Overall, vismodegib reduced the surgical defect area by 27% (95% confidence interval -45.7% to -7.9%; P=.006) from baseline. Vismodegib was not effective in patients who received less than 3 months. Over a mean follow-up of 11.5 (range 4-21) months for all tumors, only 1 tumor recurred at 17 months post-Mohs micrographic surgery.

Limitations: Short follow-up time and no placebo control are limitations.

Conclusion: Neoadjuvant vismodegib appears to reduce surgical defect area when taken for 3 months or longer for nonrecurrent BCCs in functionally sensitive locations. Further studies with larger sample sizes and long-term follow-up are warranted.

Keywords: Mohs; basal cell carcinoma; neoadjuvant; surgery; surgical defect; vismodegib.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alopecia / chemically induced
  • Anilides / adverse effects
  • Anilides / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Basal Cell / drug therapy*
  • Carcinoma, Basal Cell / pathology
  • Carcinoma, Basal Cell / surgery
  • Chemotherapy, Adjuvant
  • Dysgeusia / chemically induced
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mohs Surgery / adverse effects*
  • Muscle Cramp / chemically induced
  • Neoadjuvant Therapy
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / surgery
  • Tumor Burden

Substances

  • Anilides
  • Antineoplastic Agents
  • HhAntag691
  • Pyridines