Real-World ARON-3 Data Highlight the Advantage of Triplet Therapy in High-Volume mHSPC

At the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin,  pivotal real-world data from the international ARON-3 study were revealed, advancing treatment insights for high-volume metastatic hormone-sensitive prostate cancer (mHSPC) with bone metastases.

The ARON-3 study evaluated 841 patients receiving either doublet therapy, combining androgen deprivation therapy (ADT) with androgen receptor pathway inhibitors (ARPIs) like darolutamide or abiraterone, or triplet therapy, which adds docetaxel chemotherapy to this regimen. Using robust propensity score matching, outcomes were stratified by bone metastases burden (≤10 versus >10).

Findings revealed triplet therapy notably improved both time-to-treatment failure and overall survival in patients harboring more than 10 bone metastases or visceral metastases. Specifically, hazard ratios showed a 56% reduction in risk for treatment failure and a 50% survival benefit with triplet therapy compared to doublet treatment. Additionally, triplet therapy was linked to faster opioid reduction and improved performance status early after treatment initiation. Conversely, for patients with 10 or fewer bone metastases, doublet and triplet regimens yielded comparable outcomes, supporting treatment individualization based on metastatic burden.

Median overall survival (OS) reached 63 months with ADT plus abiraterone, while it was not reached for ADT combined with apalutamide, enzalutamide, or the triplet therapy including docetaxel plus darolutamide.

This pivotal study reinforces the survival advantage of triplet therapy in high-volume mHSPC and underscores the need to tailor therapeutic intensity according to metastatic extent. Given the complexity of metastatic prostate cancer, ARON-3’s real-world evidence provides a valuable guide for oncologists optimizing frontline treatment strategies.

In sum, the ARON-3 study validates triplet therapy as a superior option in patients with extensive bone and visceral disease, while affirming doublet therapy’s role in those with lower metastatic volume—marking an important step forward in personalized prostate cancer care.

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