Mechanisms of Action and Differentiation Among ARPI Therapies in mCSPC

Panelists discussed the mechanisms of action and distinguishing features of androgen receptor pathway inhibitors (ARPIs) used in metastatic castration-sensitive prostate cancer (mCSPC). They outlined two primary categories: the lutamides—including apalutamide, enzalutamide, and darolutamide—which inhibit androgen receptor binding, nuclear translocation, and transcription to induce tumor cell death, and abiraterone, a CYP17 inhibitor that blocks androgen synthesis at multiple sites including the testes, adrenal glands, and tumor tissue. While all ARPIs target the androgen axis, their mechanisms and clinical data differ.

Panelists noted that abiraterone, apalutamide, and enzalutamide demonstrate overall survival benefits, while darolutamide primarily delays progression. They discussed side-effect profiles and monitoring needs—highlighting the need for liver function monitoring and steroid co-administration with abiraterone—and emphasized that treatment selection often depends on balancing efficacy, toxicity, and clinician comfort.