Treatment (Rx) patterns and attrition rates in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated between 2021-2025.

Abstract

94 Background: The Rx landscape for mCRPC has shifted significantly in recent years with the introduction of poly(ADP-ribose) polymerase inhibitors (PARPi) alone, PARPi in combination with androgen receptor pathway inhibitors (ARPIs), and 177 Lu-PSMA-617 (Lu). This expansion in the Rx armamentarium increased the complexity of Rx sequencing decisions. In this analysis, we sought to assess recent Rx patterns and attrition rates in pts with mCRPC. Methods: This retrospective cohort study utilized the US-based, electronic health record-derived deidentified Flatiron Health Research Database. Eligibility: diagnosis of mCRPC and receipt of first-line (1L) Rx. The data cut-off date was 6/30/2025. The types of Rx from 1L to 5L were summarized using frequency and percentages. Subgroup analysis by the year of 1L initiation was performed. Rx was categorized into: ARPIs, taxane based therapies, PARPi-based therapies, platinum-based therapies, Lu-based therapies, radium-223, sipuleucel-T, immunotherapy, and other. Results: Overall 5,008 pts with mCRPC who received 1L Rx between 1/1/2021 and 6/30/2025 were included in the analysis. Median age was 75 years (IQR 68 – 82), 55% were White non-Hispanic, and 76% were treated in community practice. Among these, 54% received 2L Rx, and 26% received 3L. Rx trends are summarized in Table. ARPIs were the most commonly used Rx in 1L (80%) and 2L (43%), with decreasing use in subsequent lines. Taxane use increased from 12% in 1L to 34% in 2L and remained common in later lines. Use of Lu and PARPi rose in later lines. From 2021 to 2025, ARPI use in 1L decreased from 80% to 67%. Further results stratified by year will be presented at the meeting. Conclusions: In this large real-world mCRPC cohort, only about half of pts received 2L Rx, with attrition rising significantly across subsequent lines. ARPIs and taxanes remained the most common 1L Rx including 2025, with increased utilization of Lu and PARPi in later lines. These findings highlight the evolving complexity of mCRPC management and significant drop-off with later lines, underscoring the need for optimized sequencing strategies, more efficacious frontline therapies, and interventions to improve access. Rx patterns across 5 lines of therapy in pts with mCRPC. Rx, n (%) 1LN = 5,008 2LN = 2,695 3LN = 1,325 4LN = 589 5LN = 228 ARPIs 4000 (79.8) 1152 (42.6) 319 (24.1) 74 (12.6) 18 (7.9) Taxane 606 (12.1) 918 (34.1) 486 (36.6) 212 (36) 62 (27.2) Lu 108 (2.2) 178 (6.6) 203 (15.3) 138 (23.4) 69 (30.3) PARPi 100 (2) 146 (5.4) 100 (7.5) 42 (7.1) 12 (5.2) Sipuleucel-T 69 (1.4) 31 (1.2) 10 (0.8) 1 (0.2) 2 (0.9) Platinum-based Rx 50 (1) 89 (3.3) 86 (6.5) 47 (8) 25 (11) Radium-223 50 (1) 64 (2.4) 22 (1.7) 12 (2) 5 (2.2) Immunotherapy 22 (0.4) 24 (0.9) 18 (1.4) 19 (3.2) 11 (4.8) Other 3 (0.1) 93 (3.5) 81 (6.1) 44 (7.5) 24 (10.5)