Real-world patient characteristics and treatment patterns among patients with metastatic castration-resistant prostate cancer treated with talazoparib plus enzalutamide in the US.

Abstract

121 Background: Talazoparib plus enzalutamide (tala+enza) was approved by FDA in June 2023 for homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC), based on statistically significant radiographic progression-free survival from the TALAPRO-2 (TP-2) study. 8% of patients in TP-2 cohort 2 (HRR-selected) received prior abiraterone treatment during the enrollment period from 2018 to 2022. The current study evaluated HRR gene testing, clinical characteristics, and treatment patterns of patients receiving tala+enza in a real world setting. Methods: A non-interventional, retrospective cohort study of US patients with mCRPC was conducted using Flatiron Health’s electronic health record database. Adult patients were included if they initiated tala+enza between June 20, 2023 to February 28, 2025. Gene clustering hierarchy was defined as any BRCA1/BRCA2 alteration ( BRCA cluster), then any PALB2 ( PALB2 cluster), next any CDK12 ( CDK12 cluster), then any ATM ( ATM cluster). Descriptive statistics were used to summarize clinical characteristics, HRR gene testing, and treatment patterns. Results: A total of 192 adult patients with mCRPC treated with tala+enza were included. The median age was 73 years, with the majority of patients being White (62.0%) and from the South (52.1%). Nearly half (47.9%) had a Gleason score of 9-10. The median follow-up from initiation of tala+enza was 8.2 months. Of the 192 patients, 54.2% received androgen receptor pathway inhibitors (ARPi), 10.9% received apalutamide, 21.9% received enzalutamide, 29.7% received abiraterone, and 5.2% received darolutamide prior to mCRPC diagnosis. Additionally, 10.9% of patients received docetaxel prior to mCRPC diagnosis. Tala+enza was initiated during 1L for mCRPC for 39.1%, 2L for 28.6%, and 3L+ for 32.2% of patients. Of those that initiated tala+enza, 76.0% started at 0.5mg dose and 22.9% of patients had at least one dose reduction during the follow up. While 97.4% had documented HRR mutation testing during the study period, only 41.1% had a documented test prior to their mCRPC diagnosis. The most frequent HRR biomarker clusters prior to initiation of tala+enza diagnosis were ATM (27.6%), BRCA (27.1%), CDK12 (13.5%), other cluster (13.5%), PALB2 (3.1%) and 15.1% had no documented mutation or test. Conclusions: This study highlights heterogeneous treatment and HRR testing patterns among patients with mCRPC receiving tala+enza. In this real-world dataset, over half of patients had received ARPi treatment prior to mCRPC. Despite limited follow-up, these findings offer early insights into real-world use and future evaluations should investigate real world clinical outcomes.