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Introduction: Data for direct comparison of the outcomes for ADT+androgen signaling pathway-inhibitors (ARPI) vs. ADT+ARPI+docetaxel is scant, especially in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) according to CHAARTED-classification and regarding to the number of bone metastases.

Method: Relying on the multicentric international ARON-3 database, high-volume mHSPC patients with bone metastases undergoing doublet vs. triplet-therapy were selected and stratified according to the number of bone metastases (≤10 vs. >10). Primary endpoints consisted of time to treatment failure (TTF), PSA-response and overall survival (OS).

Results: Overall, 841 patients treated with doublet (75%) or triplet (25%) therapy were included. Patients undergoing triplet-therapy had a higher reduction in opioid use and a higher improvement in ECOG performance status 12 weeks after treatment initiation. Median OS was 63.0 months for ADT+ABI and was not reached for ADT+APA, ADT+ENZA and ADT+DOCE+DARO. In adjusted analyses, triplet therapy was associated with longer TTF and numerically longer OS in patients with >10 bone metastases (HR 0.44, p=0.002 and HR 0.50, p=0.048). In patients with concomitant visceral metastases, triplet therapy was associated with numerically longer TTF and OS, but differences were not statistically significant.

Conclusion: The outcome of high-volume mHSPC patients stratified by bone metastatic burden, was more favorable with triplet therapy in the >10 subgroup, whereas no meaningful differences were observed in the ≤10 subgroup. Given the retrospective design and potential residual confounding, prospective validation is warranted.