Galeterone for the treatment of advanced prostate cancer: the evidence to date

Area of Science:

• Oncology
• Pharmacology
• Genetics

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) treatment has advanced with drugs like abiraterone and enzalutamide.
• However, most patients eventually develop resistance, leading to treatment failure and death.
• Androgen receptor variant 7 (AR-V7) is a key mechanism of resistance, linked to poor outcomes with current therapies.

Purpose of the Study:

• To discuss the biological mechanisms of action of galeterone.
• To review safety and efficacy data from Phase I and II clinical studies of galeterone in mCRPC patients.
• To highlight the ongoing Phase III trial of galeterone in AR-V7-positive mCRPC patients.

Main Methods:

• Review of biological mechanisms of galeterone.
• Analysis of safety and efficacy data from Phase I and II clinical trials.
• Description of the Phase III biomarker-selected trial design.

Main Results:

• Galeterone is a novel anti-androgen with multiple mechanisms of action, including targeting full-length AR and aberrant AR like AR-V7.
• Phase I/II studies provide initial safety and efficacy data for galeterone in mCRPC.
• A Phase III trial comparing galeterone to enzalutamide in AR-V7-positive patients is underway.

Conclusions:

• Galeterone represents a potential new therapeutic option for mCRPC, particularly for patients resistant to existing treatments.
• Its ability to target AR-V7 makes it a promising agent for a difficult-to-treat patient population.
• The ongoing Phase III trial is crucial for establishing galeterone's role in mCRPC treatment.