Mechanistic Differences in ARPIs and Long-Term Clinical Outcomes in mCSPC

In this segment, panelists examined emerging long-term data on androgen receptor pathway inhibitors (ARPIs) used in metastatic castration-sensitive prostate cancer (mCSPC). They reviewed distinctions among the lutamides (enzalutamide, apalutamide, darolutamide) and abiraterone, emphasizing that while all enhance androgen suppression, abiraterone’s CYP17 inhibition introduces added metabolic and hepatic risks due to required steroid co-administration. Discussion highlighted recent ASCOreadouts, which suggested that in frailer, elderly populations, lutamides may offer superior tolerability compared with abiraterone—challenging prior assumptions. Panelists also addressed misconceptions surrounding ARPI side effects, noting that double-blind trial data (ARCHES, TITAN) show grade 3 adverse event rates and discontinuations comparable to placebo. They emphasized that clinician perceptions and communication can strongly influence how patients experience and report toxicities. Overall, the segment underscored the importance of balancing efficacy, safety, and patient perception when selecting long-term therapy for mCSPC.

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.