Comparative effectiveness of abiraterone and enzalutamide in the first-line treatment of metastatic castration-resistant prostate cancer (mCRPC): A retrospective cohort study in a large database of deeply curated EHR real-world data (RWD) from community oncology practices in the US.

Abstract

175 Background: Abiraterone(A) and enzalutamide(E), both oral androgen receptor targeted agents, are available as first-line treatment options for mCRPC patients. Direct comparisons of efficacy have not been performed for mCRPC patients primarily receiving their cancer care outside of academic centers or integrated health care systems. The study aims to evaluate the real-world effectiveness between first-line A and E-containing regimens in mCRPC patients primarily receiving care in the US community oncology setting. Methods: Patients were selected from ConcertAI Patient 360 Prostate data product, a large de-identified database of deeply curated EHR RWD, sourced from data sharing agreements with community oncology practices. mCRPC patients treated with a first-line A or E-cont. regimen between 1/2011 and 6/2022 were included. OS, TTNT, TTD outcomes were described using KM estimates and evaluated with Cox proportional hazard (HR) model. Confounding was addressed with inverse probability treatment weighting (IPTW) propensity scores based on age, BMI, ECOG, prior anti-androgen exposure, smoking status, comorbidities, and nadir PSA. Sensitivity analysis evaluated KM and HR for each covariate strata. Hazard ratios were also evaluated with multiple imputation by chained equations for missing covariates. Results: From 3,578 mCRPC patients, 1,210 (33.8%) received E-cont. regimen and 1,357 (37.9%) received A-cont. regimen(ref) with a median of 8 months duration for both drugs. Adjusted HR (aHR) for all three outcomes showed a slight increase in effectiveness for E albeit not significant (OS (aHR 0.99, CI 0.87-1.12), TTNT (aHR 0.98, CI 0.89-1.08). Adjusted model including imputation (iHR) supported unimputed results (OS (iHR 0.97, CI 0.88-1.07), TTNT (aHR 0.94, CI 0.9-1.10). The HRs for OS, TTNT and TTD in sicker patients were consistent (2+ ECOG TTNT (aHR 0.95, 0.81-1.12)), (BMI >30, TTNT (aHR 0.84, 0.61-1.18)), and reached significance for some models (2+ ECOG TTD (aHR 0.66, 0.48-0.91)). Conclusions: First-line E-cont. regimens consistently showed increased effectiveness in outcomes compared to A-cont. regimens in mCRPC patients treated in community oncology setting. The effects sizes are modest and did not reach significance, however analysis of the sickest patients showed a trend of consistently larger effect sizes which reached significance for some outcomes. More work needs to be done to evaluate if these results support findings from other RWD sources.