Range-Bounded Adaptive Therapy in Metastatic Prostate Cancer

Area of Science:

• Oncology
• Mathematical Biology
• Pharmacology

Background:

• Adaptive therapy with abiraterone acetate (AA) is an alternative to continuous treatment for metastatic castration-resistant prostate cancer (mCRPC).
• Cycling AA aims to leverage competitive suppression of resistant cancer cells by sensitive cells to prolong treatment efficacy.
• Modifications to adaptive AA may further enhance treatment outcomes for specific patient subsets.

Purpose of the Study:

• To investigate modifications to adaptive AA therapy to extend time to progression in mCRPC.
• To develop and evaluate a mathematical model for simulating adaptive AA and a modified approach called range-bounded adaptive therapy (RBAT).

Main Methods:

• A mathematical model incorporating stem cell, non-stem cell, and prostate-specific antigen (PSA) dynamics was developed.
• The model was calibrated using longitudinal PSA data from 16 mCRPC patients undergoing adaptive AA.
• Simulations compared standard adaptive AA with RBAT, where treatment is modulated to maintain PSA within patient-specific bounds.

Main Results:

• RBAT simulations demonstrated a potential to further extend time to progression compared to standard adaptive AA.
• RBAT reduced cumulative abiraterone acetate (AA) dose in 11 out of 16 patients, with reductions up to 40%.
• The model suggests RBAT can improve patient care, especially for those with suboptimal responses to conventional adaptive therapy.

Conclusions:

• Range-bounded adaptive therapy (RBAT) offers a promising modification to conventional adaptive abiraterone acetate (AA) therapy for mCRPC.
• RBAT has the potential to improve treatment duration and reduce drug exposure.
• This approach may enhance patient care and outcomes in metastatic castration-resistant prostate cancer.