Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor,...

Area of Science:

• Oncology
• Dermatology
• Pharmacology

Background:

• Vismodegib is a first-in-class Hedgehog pathway inhibitor approved for advanced basal cell carcinomas (BCCs).
• Initial FDA approval was based on a single, nonrandomized phase-II trial, necessitating further clinical data.
• There is a critical need to confirm the efficacy and safety of vismodegib in a broader patient population.

Purpose of the Study:

• To assess the efficacy and safety of vismodegib in patients with advanced BCC.
• To provide early access to vismodegib for patients with limited treatment options.
• To gather additional clinical data beyond the initial phase-II trial.

Main Methods:

• An open-label, multicenter study was conducted.
• Patients with advanced BCC, unsuitable for radiotherapy or surgery, received 150 mg of vismodegib daily.
• Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.

Main Results:

• 119 patients with advanced BCC received vismodegib for a median of 5.5 months.
• Objective response rates were 46.4% for locally advanced BCC and 30.8% for metastatic BCC.
• Prior systemic therapy was negatively associated with response in locally advanced BCC (P = .002).
• Most common adverse events included muscle spasms (70.6%), dysgeusia (70.6%), alopecia (58.0%), and diarrhea (25.2%) over a mean safety follow-up of 6.5 months.

Conclusions:

• The study provides valuable clinical data supporting the efficacy and safety of vismodegib for advanced BCC.
• Abbreviated follow-up due to study termination upon FDA approval is a noted limitation.
• Larger studies are ongoing to identify response predictors and long-term outcomes.