Darolutamide-based triplet therapy versus androgen receptor pathway inhibitor-based doublet therapy for metastatic castration-sensitive prostate cancer: a real-world analysis using the TriNetX database.

BACKGROUND: Currently, there are no large cohort studies comparing the clinical outcomes of triplet therapy with those of androgen receptor pathway inhibitor (ARPI)-based doublet therapy for patients with metastatic castration-sensitive prostate cancer (mCSPC) representing real-world practice. Therefore, the present study aimed to compare whether triplet or doublet therapy is more effective in patients with mCSPC. METHODS: This large-scale retrospective cohort study used TriNetX electronic medical record data from August 2018 to July 2026, enrolling patients with mCSPC categorized as receiving triplet [darolutamide + docetaxel + androgen deprivation therapy (ADT)] or doublet therapy (enzalutamide or apalutamide + ADT). The primary outcome was overall survival (OS), while the secondary outcome was the proportion of patients achieving a PSA level ≤ 0.2 ng/ml. Propensity score matching (PSM) (1:1) was conducted to adjust for confounding variables between groups. RESULTS: Overall, 1841 patients met the eligibility criteria. Following PSM (n = 329), triplet therapy was associated with a statistically significant improvement in OS compared with doublet therapy (hazard ratio: 0.601; 95% confidence interval: 0.420-0.862; log-rank P = .005). The proportions of patients achieving PSA ≤0.2 ng/ml were 26.4% vs. 17.0% at 3 months (P = .003), 37.4% vs. 27.7% at 6 months (P = .008), 43.8% vs. 35.9% at 12 months (P = .038), and 50.5% vs. 40.1% at any time (P = .008) in the triplet and doublet groups, respectively. CONCLUSIONS: In this real-world analysis using the TriNetX database, triplet therapy including darolutamide significantly improved OS and PSA decline compared with ARPI-based doublet therapy.