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N Basset-Seguin1

  • 1Université Paris-7, service de dermatologie, hôpital Saint-Louis, Paris, France.

Annales De Dermatologie Et De Venereologie
|November 28, 2018
PubMed
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New hedgehog pathway inhibitors, vismodegib and sonidegib, offer targeted treatment for advanced basal cell carcinoma (BCC). While effective, long-term use is limited by side effects, with immunotherapy as a future hope.

Area of Science:

  • Oncology
  • Dermatology
  • Pharmacology

Background:

  • Advanced basal cell carcinoma (BCC) historically lacked effective treatments, relying on disfiguring surgery or unproven chemotherapy.
  • Radiotherapy is often not feasible due to prior treatment or lesion characteristics.
  • The sonic hedgehog pathway's role in BCC pathogenesis led to targeted therapies.

Purpose of the Study:

  • To compare the efficacy and safety of vismodegib and sonidegib for advanced BCC.
  • To review the pharmacokinetic profiles and clinical outcomes of these hedgehog pathway inhibitors.

Main Methods:

  • Review of pivotal Phase II studies for vismodegib and sonidegib.
  • Analysis of objective response rates (ORR) and adverse event profiles.
  • Comparison of drug pharmacokinetics and long-term tolerability.
Keywords:
Advanced BCCCBC avancésHedgehog pathwayImmunotherapyImmunothérapieSonidegibSonidégibVismodegibVismodégibVoie Hedgehog

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Main Results:

  • Vismodegib showed an ORR of 47.6% at 21 months; sonidegib demonstrated an ORR of 56.1% at 18 months.
  • Both drugs share similar adverse event profiles, often leading to treatment discontinuation.
  • Drug resistance is rare, but a significant concern for long-term management.

Conclusions:

  • Vismodegib and sonidegib represent significant advancements in treating advanced BCC.
  • Hedgehog pathway inhibitors offer improved outcomes but face challenges with long-term tolerability.
  • Immunotherapy is a promising future direction for managing resistant or intolerant BCC cases.