Darolutamide versus abiraterone acetate-based triplets in patients with hormone-sensitive prostate cancer: real-world, head-to-head comparison from the ARON-3 study.

BACKGROUND

The therapeutic landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has expanded significantly with triplet regimens, raising questions about their real-world applicability. This study evaluates the efficacy and safety of darolutamide- and abiraterone-based triplets using real-world data from the ARON-3 study.

METHODS

A retrospective analysis was conducted on 247 mHSPC patients treated with DARO+DOCE+ADT or ABI+DOCE+ADT across 37 institutions in 14 countries. Key outcomes included progression-free survival (PFS), overall survival (OS), PSA kinetics, and safety. A propensity score was estimated based on key clinical variables and included as a covariate in Cox regression models to adjust for baseline imbalances between treatment groups.

RESULTS

Data from 247 patients receiving triplet therapy were analyzed. The median OS for the entire cohort was not reached (NR). The median PFS was 24.8 months (95% CI: 18.7-33.6), with NR for DARO+DOCE+ADT and 21.5 months (95% CI: 13.1-25.2) for ABI+DOCE+ADT (P=0.007). In patients with visceral metastases, DARO+DOCE+ADT demonstrated superior outcomes, achieving higher OS rates at 6 months (97% vs. 83%, P=0.002) and 12 months (92% vs. 74%, P<0.001) compared to ABI+DOCE+ADT. The safety profiles of both regimens were comparable, although grade 3-4 fatigue was more frequently observed in the ABI+DOCE+ADT group. After adjusting for baseline imbalances through propensity score inclusion in multivariate models, the differences in OS (P=0.103) and PFS (P=0.135) between treatment groups did not reach statistical significance, although a numerical trend favoring DARO+DOCE+ADT was observed.

CONCLUSIONS

Both regimens demonstrate efficacy, with DARO+DOCE+ADT offering superior outcomes in high-volume disease, especially visceral metastases. Nonetheless, the limited sample size and potential biases highlight the need for further follow-up and biomarker-driven studies in larger cohorts to refine treatment strategies.