Management of metastatic castration-resistant prostate cancer (mCRPC) at the Veterans Affairs Healthcare System (VAHCS): A real-world assessment of patient characteristics and treatment across lines of therapy.
Authors: Zheng Renning , Nguyen Jennifer , Patel Jeetvan , Bollu Vamsi , Kang Barinder , De Hoedt Amanda Marie , Parrish Joshua , Cummings Stirling , Freedland Stephen J. , Nguyen Anthony Tuan 
Published: February 2025

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Background:
With the emergence of several newly approved therapies for mCRPC, data on the optimal treatment sequence are limited. The aim of this study is to understand the treatment patterns of mCRPC patients who received at least one androgen receptor pathway inhibitor (ARPI) or taxane at the VAHCS, an equal-access healthcare system.
Methods:
This is a retrospective, observational study utilizing VAHCS claims data from patients diagnosed with mCRPC between January 1, 2018 and February 29, 2024 nationwide. Patients with mCRPC who received first-line (1L) therapy of ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide; [ARPI cohort]) or a taxane (docetaxel or cabazitaxel; [taxane cohort]) were included; 1L therapy was defined as the first prescription for ARPI or taxane after prostate cancer diagnosis. Thus, though the 1L treatment could have been for metastatic castration-sensitive prostate cancer or mCRPC, all patients ultimately progressed to mCRPC. Patients who received radiation within 6 months or any other chemotherapy prior to 1L therapy, or who were diagnosed with any other cancers (excluding non-melanoma skin cancer) prior to mCRPC were excluded.
Results:
In total, 2982 patients with mCRPC who met the inclusion criteria were identified, which included a large cohort of African American patients (25%). Although most patients received an ARPI in the 1L (2828 patients, 95%), 154 patients (5%) received 1L taxane. Patients in the ARPI cohort were significantly older than those in the taxane cohort (median 74 vs 68 years; p<0.001). Patients in the ARPI cohort received mainly 1L abiraterone or enzalutamide with a similar frequency (both 48%), and docetaxel was the most common treatment for patients who had received 1L taxane (97%). Overall, 1223 patients (41% of all patients) received second-line (2L) therapy. Taxanes were more frequently used in 2L treatment (16%) compared with 1L; however ARPI, especially abiraterone (27%) and enzalutamide (42%), remained the most frequent choices for 2L treatment. Back-to-back ARPI use in 1L and 2L was the most common treatment sequence, with 74% of patients who received 2L abiraterone having been treated with 1L enzalutamide, and 87% of patients who received 2L enzalutamide having been treated with 1L abiraterone. Few patients (11% of all patients) received third-line (3L) treatments.
Conclusions:
In the VA equal-access healthcare system, back-to-back ARPIs remained the most common treatment sequence for the management of patients with mCRPC with few patients receiving 3L treatment. Further research is planned to investigate clinical outcomes, adverse events, and healthcare resources utilization associated with these treatment sequences to hopefully identify an optimal mCRPC management.