Abstract IA015: Exploring how competition can be leveraged to improve adaptive therapy in metastatic prostate cancer

Abstract

Abstract Prostate cancer remains the most prevalent cancer in men in the US. While continuous first-line hormone treatment at maximum tolerable dose is the standard of care, continuous treatment often selects for the resistant phenotypes resulting in castration resistant disease. Second-line hormone therapy options, such as abiraterone acetate (AA), have been proven effective for metastatic castration resistant prostate cancer (mCRPC). Adaptive AA, whereby treatment is cycled on and off using patient-specific treatment triggers, has been shown to be effective at reducing toxicity and prolonging time to progression. It is hypothesized that cycling through treatment allows sensitive cells to competitively suppress resistant cells, thereby increasing the amount of time that treatment is effective. It has been proposed that there exists a subset of patients for which this competition can be enhanced through slight modifications to adaptive AA. Here, we investigate this by calibrating a simple mathematical model to longitudinal prostate-specific antigen data from 16 mCRPC patients undergoing adaptive AA. Model parameters are used to simulate modified adaptive therapy and compare against conventional adaptive therapy. Model simulations show that modified adaptive therapy can extend time to progression, while reducing the cumulative dose patients receive. This is a promising first step in improving patient care, particularly in those patients who do not respond well to conventional adaptive therapy. Citation Format: Renee Brady-Nicholls, Heiko Enderling. Exploring how competition can be leveraged to improve adaptive therapy in metastatic prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA015.