Real-world time-to-castration resistance (CR) among patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) initiating apalutamide (APA), enzalutamide (ENZ), or abiraterone acetate (ABI) from an oncology database.

65 Background: CR is an important clinical indicator of disease progression and worsening overall survival among pts with mCSPC. This study describes real-world time-to-CR progression in an oncology setting among pts with mCSPC who initiated APA, ENZ, or ABI in the United States. Methods: Clinical data from the Flatiron Metastatic Prostate Cancer (PC) Core Registry Electronic DataMart (1/1/2013 – 07/31/2022) were evaluated. Metastatic pts without evidence of CR before initiating a next-generation androgen inhibitor (AAI) were classified into exclusive treatment cohorts based on the start date (index date) for APA, ENZ, or ABI. CR was identified by a Flatiron algorithm searching for: 1) mention of CR in patient charts, 2) rising prostate-specific antigen (PSA) levels documented from laboratory testing, or 3) mention of rising PSA while on hormonal therapy from unstructured data sources. Pts had ≥12 months (mo) of clinical data pre-index date and were followed from the index date until the end of clinical activity (including death) or data availability. The proportion of pts developing CR was described separately for each cohort using Kaplan-Meier analysis up to 24 mo post-index, with no adjustment for baseline confounders. CR progression rates in the current analysis were descriptively compared to those observed in Phase 3 trials where available. Results: A total of 155 APA, 385 ENZ and 711 ABI pts were evaluated. Mean age at index was ~73 years in each group. Mean follow-up was 12.8 mo (APA), 13.4 mo (ENZ) and 20.6 mo (ABI). Use of androgen deprivation therapy prior to initiation of AAI was observed in ~85% of pts. The median time between documented metastasis and the index date was 2.3 mo (APA), 2.8 mo (ENZ), and 2.3 mo (ABI). Progression rates to CR are shown. By 24 mo, the median time-to-CR was not reached with any treatment studied. By 24 mo, progression to CR was observed in 26% of APA pts in this analysis (32% in TITAN); 36% of ENZ pts in this analysis (25% in ARCHES); and 33% of ABI pts in this analysis (progression to CR not reported in LATITUDE). Conclusions: In this real-world database, the observed proportions of pts progressing to CRPC for the APA and ENZ cohorts were generally consistent with results of Phase 3 trials and include a small proportion of pts with early progression to CRPC. Increased physician awareness of the benefits of early initiation of an AAI along with identification of baseline biomarkers associated with early progression to CRPC may improve clinical outcomes. [Table: see text]