Doublet Versus Triplet Therapy in High-volume Metastatic Hormone-sensitive Prostate Cancer Patients with Bone Metastases: Results from the ARON-3 Study.

BACKGROUND AND

OBJECTIVE

Data for direct comparison of the outcomes for androgen-deprivation therapy (ADT) + androgen signaling pathway-inhibitors (ARPI) versus ADT + ARPI + docetaxel are 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.

DESIGN, SETTING AND PATICIPANTS: Relying on the multicentric international ARON-3 database, patients with high-volume mHSPC with bone metastases undergoing doublet versus 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), prostate-specific antigen-response, and overall survival (OS).

RESULTS AND LIMITATIONS: Overall, 841 patients treated with doublet (75%) or triplet (25%) therapy were included. At 12 wk, triplet therapy was associated with changes in opioid use and in Eastern Cooperative Oncology Group performance status. Median OS was 63.0 mo for ADT + abiraterone acetate and was not reached for ADT + apalutamide, ADT + enzalutamide, and ADT + docetaxel + darolutamide. Differences in adjusted TTF estimates between treatment groups were observed in patients with >10 bone metastases (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.28-0.87; p = 0.02), whereas adjusted OS estimates also differed numerically but were not statistically significant (HR 0.48, 95% CI 0.21-1.07; p = 0.1). In patients with concomitant visceral metastases, TTF and OS estimates also differed numerically by treatment group; however, these differences were not statistically significant.

CONCLUSIONS

In exploratory subgroup analyses, TTF and OS estimates varied by bone metastatic burden, but formal interaction testing did not show evidence of heterogeneity. These findings require prospective validation.