Comparative effectiveness of doublet versus triplet therapy in high-volume metastatic hormone-sensitive prostate cancer: A real-world evidence study.

Abstract

e17084 Background: Although the combination of androgen deprivation therapy (ADT) with an androgen receptor pathway inhibitor (ARPI) is the established standard of care for patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC), the added benefit of intensifying therapy with docetaxel to create a triplet regimen remains undefined. In the absence of direct comparative randomized trial data, real-world evidence (RWE) is crucial to inform this treatment intensification decision. Methods: Our multicenter retrospective study included patients with high-volume mHSPC (by CHAARTED criteria) who initiated doublet (ADT + ARPI) or triplet (docetaxel + ADT + ARPI) therapy between 2022 and 2024. To mitigate confounding, patients were matched using cardinality matching at a 2:1 ratio. The primary endpoint was 2-year progression-free survival (PFS). Secondary end-points was overall survival (OS). PFS was defined as the time from treatment initiation to clinical/radiological progression, commencement of subsequent systemic therapy, or death from any cause. Results: Of 183 patients 122 received triplet (ADT+docetaxel+abiraterone or ADT+docetaxel+enzalutamide), 61 doublet therapy (ADT+enzalutamide or apalutamide). The triplet regimen demonstrated superior outcomes: 2-year PFS was 75.9% vs. 48.9% (HR 0.50, 95% CI 0.31–0.80) and 2-year OS was 82.9% vs. 66.8% (HR 0.47, 95% CI 0.28–0.79). The benefit of docetaxel addition was pronounced in patients aged < 65 years (PFS: HR 0.28, 95% CI 0.12-0.68; OS: HR 0.17, 95% CI 0.06-0.54), patients with liver metastases (PFS: HR 0.16, 95% CI 0.04-0.68; OS: HR 0.12, 95% 0.02-0.61), Gleason score ≥8 (PFS: HR 0.49, 95% 0.29-0.82; OS: HR 0.45, 95% CI 0.25-0.84) and detectable baseline erythroblasts in blood sample (PFS: HR 0.29, 95% CI 0.11-0.76; OS: HR 0.24, 95% CI 0.07-0.77). No significant survival difference between triplet and doublet therapy was found in patients > 65 years or with metachronous high-volume disease. Conclusions: Real-world data confirms the superiority of triplet therapy for the majority of patients with synchronous high-volume mHSPC. Treatment intensification can be effectively guided by routine clinical characteristics.