Darolutamide Versus Abiraterone-Based Triplets in mHSPC: Real-World Signals from the ARON-3 Study

Using data from the international ARON-3 real-world study, investigators performed a retrospective head-to-head comparison of darolutamide- and abiraterone-based triplet therapy in patients with metastatic hormone-sensitive prostate cancer.

The comparison included 247 patients treated with darolutamide plus docetaxel plus androgen deprivation therapy or abiraterone plus docetaxel plus androgen deprivation therapy across 37 institutions in 14 countries. In the overall cohort, median overall survival was not reached, and median progression-free survival was 24.8 months. In the unadjusted analysis, progression-free survival appeared longer with the darolutamide-based triplet, with median PFS not reached versus 21.5 months for the abiraterone-based regimen.

However, after adjustment for baseline imbalances using a propensity score in multivariable models, differences in overall survival and progression-free survival were no longer statistically significant, although the numerical trend still favored darolutamide.

The subgroup findings are what make the study especially relevant. Patients with visceral metastases appeared to derive the clearest benefit from darolutamide-based triplet therapy, with higher overall survival rates at both 6 months and 12 months compared with the abiraterone-based triplet, suggesting that darolutamide may be particularly active in biologically aggressive disease. The study also reported superior outcomes for darolutamide in high-volume disease, reinforcing the possibility that treatment differences become more visible when tumor burden is greater and prognosis is poorer.

Safety was generally comparable between the two triplet regimens, which supports the feasibility of both approaches in routine oncology practice. The main difference highlighted was a higher rate of grade 3 to 4 fatigue in the abiraterone-based group, while no major overall safety separation was reported. Taken together, ARON-3 suggests that darolutamide-based triplet therapy may be especially attractive in high-volume and visceral metastatic subgroups, but the findings still need confirmation in larger and better-balanced real-world or prospective datasets before they can redefine treatment preference.

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