Patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/2 alterations are eligible to receive poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as single agents or in combination with an androgen receptor pathway inhibitor after these agents showed survival improvement in their landmark clinical trials. However, data are limited regarding the uptake of PARP inhibitors in these patients.
To investigate the use of PARP inhibitors in patients with mCRPC harboring BRCA1/2 alterations.
This retrospective cohort study used the deidentified Flatiron-Health electronic health record-derived database of US community and academic practices to extract patient-level data. The data cutoff date was May 31, 2024. Patients with mCRPC with evidence of harboring BRCA1/2 alterations and alive after August 15, 2020 (ie, 3 months after the approval of the first PARP inhibitor, rucaparib, in mCRPC) were included. Statistical analysis was performed from September 2024 to May 2025.
Age, race and ethnicity, insurance status, and practice type at the time of mCRPC diagnosis.
The receipt of PARP inhibitors. Multivariable logistic regression was conducted to assess the association between the exposures and the main outcome.
Of 24 105 patients with metastatic prostate cancer, 443 male patients (median [IQR] age, 72 [65-79] years) had mCRPC with BRCA1/2 alterations and were eligible and included in our analysis. Of these patients, 227 (51.2%) received a PARP inhibitor, whereas 216 (48.8%) did not. Compared with patients covered by a commercial health plan, those covered by Medicare were significantly more likely to receive a PARP inhibitor (odds ratio, 1.91; 95% CI, 1.02-3.66; P = .047). The odds of receiving a PARP inhibitor were not significantly higher in patients treated in community practice compared with those treated in academic centers (odds ratio, 1.64; 95% CI, 1.00-2.70; P = .05).
This retrospective cohort study of patients with mCRPC and evidence of BRCA1/2 alterations found that approximately half of patients did not receive PARP inhibitors despite evidence of survival improvement in this population. These findings highlight the need to increase awareness of the survival data and access to life-prolonging therapies in patients with mCRPC.
JAMA network open. 2025 Oct 01*** epublish ***
Micah Ostrowski, Yeonjung Jo, Chadi Hage Chehade, Zeynep Irem Ozay, Georges Gebrael, Nicolas Sayegh, Edwin Lin, Ayana Srivastava, Abigail Gordhamer, Richard Ji, Haoran Li, Vinay Mathew Thomas, Sumati Gupta, Irbaz Bin Riaz, Benjamin L Maughan, Soumyajit Roy, Neeraj Agarwal, Umang Swami
Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City., Cancer Biostatistics, Huntsman Cancer Institute, University of Utah, Salt Lake City., Division of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, Westwood., Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona., Department of Radiation Oncology, UH Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio.