Dr Bryce on the Comparative Efficacy of ARPIs Regardless of Disease Volume or Timing of Metastases in mHSPC

"If you really only take away one point [from the study, it] is that on the macro level, all ARPIs performed similarly [in terms of efficacy]. The message for the [oncologist is thatthey] need to think about comorbidities and patient-specific factors when choosing amongst the various ARPIs."

Alan H. Bryce, MD, the chief clinical officer, a professor in the Department of Molecular Medicine at the Translational Genomics Research Institute, and an oncologist at City of Hope Cancer Center Phoenix, discusses the comparative efficacy of androgen receptor pathway inhibitors (ARPIs) in patients with metastatic hormone-sensitive prostate cancer (mHSCPC) according to disease volume and timing of the development of metastases.

Using the living interactive evidence synthesis framework, investigators conducted a living systematic review of ARPI efficacy in patients with mHSPC, incorporating data from phase 3 randomized controlled trials evaluating treatment intensification with abiraterone acetate (Zytiga), apalutamide (Erleada), darolutamide (Nubeqa), and enzalutamide (Xtandi). Findings presented at the 2025 Genitourinary Cancers Symposium indicated that, at a macro level, ARPIs demonstrate largely similar efficacy outcomes to each other, Bryce reports. Mixed treatment comparisons showed no significant differences in radiographic progression-free survival based on disease volume and timing of the development of metastases. Additionally, the addition of darolutamide to androgen deprivation therapy did not confer superiority over other ARPIs, he states.

Although cross-trial comparisons and network meta-analyses have limitations, evidence suggests that enzalutamide may offer a slight benefit over abiraterone acetate plus prednisone for patients with low-volume or de novo metastatic disease, Bryce notes. However, this difference is marginal, he cautions.

Given the comparable efficacy between ARPIs, selection should be driven by drug- and patient-specific factors, including toxicity profiles, cost, and accessibility, Bryce says. The most meaningful clinical decision-making will center on choosing the agent with the most favorable adverse effect profile for the individual patient rather than expecting substantial differences in prostate cancer outcomes, Bryce concludes.