Is there an optimal sequential order to androgen receptor axis therapeutics?

The hormonal therapeutic landscape in prostate cancer has expanded greatly over the last few decades with the advent of abiraterone acetate and second-generation antiandrogens such as enzalutamide, darolutamide, and apalutamide. These agents are superior to first-generation antiandrogens because they are more effective at blocking the androgen receptor signaling pathway and can overcome many of the resistance mechanisms that limited first-generation antiandrogens. With the growing number of available treatments, questions have arisen regarding patient-specific factors influencing medication selection, stage-specific use, and strategies for combination therapy and sequencing. This manuscript is intended to provide a comprehensive review of the landmark clinical trials that led to the US Food and Drug Administration approval of abiraterone and second-generation antiandrogens in various settings of prostate cancer, along with real-world off-label prescribing practices. Additionally, the article offers insight into the optimal sequencing of antiandrogens based on current data.