Real-world PSA kinetics and depth of response with ARPI-based triplet therapy in metastatic hormone-sensitive prostate cancer: A single-center retrospective cohort analysis.

Abstract

e17089 Background: Triplet therapy combining an androgen receptor pathway inhibitor (ARPI) with androgen deprivation therapy (ADT) and docetaxel has demonstrated survival benefits in phase III trials (ARASENS, PEACE-1) for metastatic hormone-sensitive prostate cancer (mHSPC). However, real-world evidence on the pace and depth of prostate-specific antigen (PSA) response remains sparse, especially in clinical practice settings outside trials. This study aimed to describe PSA kinetics and response rates in patients receiving darolutamide- or abiraterone-based triplet therapy in routine care. Methods: In this retrospective single-center cohort study, patients with mHSPC who initiated darolutamide- or abiraterone-based triplet therapy and had serial PSA measurements were included. PSA50 (≥50% decline), PSA90 (≥90% decline), and PSA < 0.2 ng/mL were evaluated. Time-to-event endpoints were estimated using Kaplan–Meier analysis. Subgroup analyses were performed by ARPI type. Results: Among 36 eligible patients (darolutamide: n = 26; abiraterone: n = 10), median age was 67 years, all had Gleason score ≥8, and baseline median PSA was 423.4 ng/mL. Metastatic burden was high: 100% bone, 80.6% lymph node, and 38.9% visceral involvement. With a median follow-up of 7.5 months, 94.4% achieved both PSA50 and PSA90, and 58.3% attained PSA < 0.2 ng/mL. Median time to PSA50 was 0.8 months (95%CI 0.6–1.0), to PSA90 was 1.1 months (95%CI 0.8–1.4), and to PSA < 0.2 ng/mL was 6.0 months (95%CI 4.0–8.0). In ARPI-specific analyses, darolutamide-treated patients (n = 26) all achieved PSA50/90, with 61.5% reaching PSA < 0.2 ng/mL at a median of 6.0 months (95%CI 4.1-7.9). In the abiraterone group (n = 10), 80% achieved PSA50/90 and 50% reached PSA < 0.2 ng/mL. Conclusions: In this real-world cohort of mHSPC patients with high-volume disease, ARPI-based triplet therapy induced rapid and deep PSA responses, consistent with clinical trial data. PSA kinetics appeared to differ between ARPI subtypes, with darolutamide associated with numerically faster and higher rates of deep PSA decline. These findings underscore the clinical activity of triplet regimens in practice and highlight PSA monitoring as a potential early indicator of treatment response. These findings are descriptive and limited by the retrospective design and small sample size.