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Sustained Suppression of Gorlin Syndrome-Associated Basal Cell Carcinomas with Vismodegib or Sonidegib: A Case Series

Raquel Wescott1, Wolfram Samlowski1,2,3

  • 1School of Medicine, University of Nevada, Reno, NV 89557, USA.

Current Oncology (Toronto, Ont.)
|October 27, 2023
PubMed

Insights

Hedgehog inhibitors like sonidegib and vismodegib effectively treat Gorlin syndrome, significantly reducing new basal cell cancers. Sustained treatment suppresses tumor progression and improves patient outcomes.

Area of Science:

  • Oncology
  • Dermatology
  • Genetics

Background:

  • Nevoid basal-cell carcinoma syndrome (Gorlin syndrome) is a genetic disorder characterized by numerous basal cell carcinomas.
  • Mutations in the hedgehog signaling pathway drive tumor development in Gorlin syndrome.
  • Vismodegib and sonidegib are targeted therapies inhibiting the hedgehog pathway.

Purpose of the Study:

  • To evaluate the efficacy and toxicity of sonidegib and vismodegib in patients with Gorlin syndrome.
  • To assess the reduction in new basal cell carcinoma development and the durability of response.
  • To analyze treatment modifications and their impact on tolerance and efficacy.

Main Methods:

  • Retrospective analysis of 10 Gorlin syndrome patients treated with sonidegib (n=6) or vismodegib (n=4) from March 2012 to March 2022.
  • Assessment of new tumor development before and during treatment.
  • Evaluation of treatment response duration, toxicity, and need for dose adjustments.

Main Results:

  • All patients achieved complete remission with hedgehog inhibitor treatment.
  • A significant reduction in new basal cell cancers was observed, from a mean of 28.3 to 1.4 per patient (p=0.0048).
  • Median follow-up was 30.7 months, with a median time to new cancer development of 47.3 months. Three patients had recurrences, and six required treatment modifications for toxicity.

Conclusions:

  • Sustained hedgehog inhibitor therapy effectively suppresses the progression of basal cell carcinomas in Gorlin syndrome.
  • Adjusting drug administration schedules can improve treatment tolerance without compromising efficacy, potentially prolonging response duration.
  • Hedgehog inhibitors represent a promising therapeutic option for managing Gorlin syndrome, though drug resistance and toxicity require careful monitoring.
Keywords:
Gorlin syndromePTCH mutationhedgehog inhibitorsnevoid basal cell carcinoma syndromesonidegibvismodegib

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