Real-world treatment patterns in patients with BRCA 1/2-positive (BRCA+) metastatic castration-resistant prostate cancer (mCRPC) initiating first-line (1L) therapy.
Authors: Bilen Mehmet Asim , Khilfeh Ibrahim , Li Kevin H , Rossi Carmine , Muser Erik , Diaz Lilian , Morrison Laura , Hilts Annalise , Lefebvre Patrick , Pilon Dominic , George Daniel J. 
Published: January 2024

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Background: Patients with BRCA+ mCRPC have an aggressive disease course. Recently, they have been shown to be responsive to treatment with poly ADP-ribose polymerase inhibitors, such as niraparib, olaparib, and rucaparib, used in combination with abiraterone acetate and prednisone or prednisolone, or as monotherapy. This study aimed to describe real-world treatment patterns and outcomes among patients with BRCA+ mCRPC. Methods: De-identified electronic health records from the Flatiron Health – Foundation Medicine Inc. (FMI) Metastatic PC Clinico-Genomic Database (01/01/2011 – 06/30/2022) were used to select BRCA+ mCRPC patients initiating 1L therapy on or after 01/01/2019 or monotherapy with androgen deprivation therapy (ADT). Patients were classified as recipients of ADT monotherapy if they used ADT at mCRPC diagnosis and did not initiate any subsequent advanced PC therapy. Distribution, line of therapy (LOT) sequences, and reasons for censoring were described in 1L, and among patients who advanced to second-line (2L) therapy. Flatiron Health and FMI did not participate in data analyses. Results: A total of 98 treated patients with BRCA+ mCRPC were included (mean age 72 years, 58% White, 15% Black, 55% Medicare-insured), 19 of whom received ADT monotherapy (mean age 70 years, 53% White, 26% Black, 47% Medicare-insured). The top five treatment regimens for mCRPC were ADT monotherapy (19%), enzalutamide (ENZ; 14%), olaparib (OLA; 13%), abiraterone acetate (AA; 11%), and docetaxel (DOC; 10%), with 14% of patients receiving ≥1 medication. The main reasons for censoring in patients with ADT monotherapy were death (52.6%), loss to follow-up (26.3%), and end of data availability (21.1%). Among the 79 patients treated with other than ADT monotherapy in 1L, 43.0% (n=34) did not advance to 2L, of which 35.3% were lost to follow-up, 29.4% died (median time-to-death: 2.25 months), 29.4% were censored at the end of data availability, and 5.9% initiated a clinical trial drug. The most prescribed 2L therapies were DOC (22.2%), OLA (20.0%), AA (13.3%), and ENZ (11.1%). In those who advanced to 2L (n=45), the most common 1L → 2L treatment sequences were OLA → DOC (11.1%), ENZ → DOC (6.7%), AA → ENZ (6.7%), and AA → OLA (6.7%). In patients receiving 2L, 51.1% (n=23) did not advance to third-line therapy, of which 34.8% died, 34.8% were lost to follow-up, 26.1% were censored at the end of data availability, and 4.3% initiated a clinical trial drug. Conclusions: Among treated patients with BRCA+ mCRPC, ADT monotherapy, ENZ, OLA, AA, and DOC were most commonly used. The majority of ADT monotherapy patients died, while a substantial proportion of patients initiating 1L therapy died or initiated a clinical trial drug and did not advance to 2L, suggesting unmet need for more effective 1L treatment for patients with BRCA+ mCRPC.