Real-world characteristics, homologous recombination repair mutation (HRRm) testing, treatment patterns, and outcomes of patients with metastatic castration-sensitive prostate cancer (mCSPC) in the US community oncology setting.

Abstract

5080 Background: Homologous recombination repair mutation (HRRm) testing is recommended by NCCN guidelines for metastatic castration-sensitive prostate cancer (mCSPC). The real-world CAPTURE study is one of the first to associate HRRm carriers with worse outcomes. However, real-world data to quantify prognostic and predictive value of HRRm in mCSPC are limited and heterogeneous, especially for patients treated within US community oncology settings. Methods: This was a retrospective observational cohort study of patients with documentation of HRRm testing who initiated systemic therapy for mCSPC (index) between 1/1/2019-3/31/2024 in The US Oncology Network or non-Network practices. Stratified random samples of 150 patients with HRRm and 150 patients without HRRm were selected for chart abstraction to collect patient characteristics within 60 days prior to index and prostate cancer treatments (androgen deprivation therapy, ADT; androgen receptor pathway inhibitors, ARPi; docetaxel, DOC) through the end of follow-up (3/31/2025). Somatic and/or germline testing results for a 12-gene HRRm panel (ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C) were recorded from all available records. Descriptive Kaplan-Meier analyses of overall survival (OS) and real-world progression-free survival (rwPFS) were assessed per HRRm, de novo metastatic and high-volume disease (HVD) status. Results: Overall, 300 patients were selected with median (IQR) age of 69 (63-77) years and median (IQR) follow-up of 25 (15-36) months. Among patients with available data at baseline, most were Gleason ≥8 (79% of 181) and PSA >4 ng/mL (85% of 274). In the HRRm cohort (N=150), 70 (47%) patients were BRCAm and 80 (53%) patients had non-BRCAm HRRm mutations. De novo mCSPC was identified in 97 (65%) patients with HRRm and 100 (67%) patients without HRRm. HVD was observed in 85 (57%) patients with HRRm and 96 (64%) without HRRm. Frontline (index) systemic therapies for mCSPC in the HRRm/non-HRRm subgroups included ADT (28%/22%), ADT+ARPi (39%/47%), ADT+DOC (15%/15%) and ADT+ARPi+DOC (15%/15%). Outcomes are summarized below. Conclusions: Patients with HRRm mCSPC experienced numerically shorter OS and rwPFS than non-HRRm patients. This highlights an important need for early HRRm testing and targeted treatment strategies within earlier disease settings. Outcome, median (95% CI), months HRRm (N=150) No HRRm(N=150) OS, overall 44.0 (36.8-55.2) 48.5 (40.2-NR) rwPFS, overall 17.5 (14.4-22.1) 22.6 (17.9-33.4) N (%), de novo 97 (65) 100 (67) OS, de novo 41.7 (30.6-44.9) 48.5 (33.4-69.4) rwPFS, de novo 15.4 (13.0-23.1) 22.0 (17.2-32.3) N (%), HVD 85 (57) 96 (64) OS, HVD 44.4 (36.8-55.2) 42.5 (33.4-69.4) rwPFS, HVD 17.7 (12.0-27.3) 19.2 (16.3-30.3)