Experts say it’s concerning that nearly half of men with metastatic castration-resistant prostate cancer who are eligible for PARP inhibitors – which could improve their survival – do not get them, and that barriers like finances and education could be preventing their use.
Healio reports that approximately half of men with metastatic castration-resistant prostate cancer and BRCA1 or BRCA2 mutations do not receive these medications.
Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors have been FDA-approved for treatment of metastatic castration-resistant prostate cancer for men with these genetic alterations, said Umang Swami, MD, MSCI, FASCO, associate Professor at University of Utah Huntsman Cancer Institute.
PARP inhibitors improve survival
Around 25% of men with advanced prostate cancer have alterations in the homologous recombinant repair pathway, and these alterations have been associated with worse outcomes for metastatic castration-resistant disease, according to study background.
The most common alterations are BRCA1 and BRCA2 mutations, which occur in 13% of patients with prostate cancer.
Phase 3 trials have shown PARP inhibitors improved survival for men with metastatic castration-resistant prostate cancer and pathway alterations, particularly BRCA1 and BRCA2 mutations.
These drugs have garnered FDA approval as monotherapy, including olaparib (Lynparza, AstraZeneca) and rucaparib (Rubraca; pharma&, Tolmar), or with androgen receptor pathway inhibitors, such as abiraterone (Zytiga, Janssen) with niraparib (Zejula, GSK), enzalutamide (Xtandi; Astellas Pharma, Pfizer) with talazoparib (Talzenna, Pfizer), and abiraterone with olaparib.
Healio previously reported on research from Swami and colleagues that showed less than half of patients with metastatic prostate cancer receive next-generation sequencing.
“When we found this out, the next question that came to mind was, what happens in the patients who actually get tested and are found to have a qualifying mutation?” Swami said.
They used the Flatiron-Health electronic health record to investigate. Analysis included 443 men (median age, 72 years, interquartile range, 65-79; 61.6% white) with metastatic castration-resistant prostate cancer with BRCA1 or BRCA2 mutations.
PARP inhibitor use served as the primary endpoint.
No justification for limited use
In all, 51.2% of patients received PARP inhibitors. “That was very surprising,” Swami said.
Men who had Medicare or other government insurance programmes had a significantly higher likelihood of receiving PARP inhibitors than those covered through commercial plans (OR = 1.91; 95% CI, 1.02-3.66), but researchers did not observe any differences based on race or practice type.
Swami and colleagues acknowledged study imitations, including its retrospective design and the possibility of undocumented next-generation sequencing testing.
The next step in research is to determine why patients may not be receiving PARP inhibitors.
Swami suggested possibilities, including clinicians being unaware of the survival benefits of these drugs, financial challenges such as high co-pays, or comorbidities.
“There may be some reasons, but even if we look at all of these reasons, it doesn’t justify that almost half of these patients are not getting these therapies,” he added.
Qualitative surveys of oncologists could offer insight into the barriers of PARP-prescribing, but a potential solution would be better integration of genomic testing into electronic health records (EHRs).
“It’s always possible that these tests may not be stored in a format where it’s readily available for the physicians to look when the patient is progressing,” Swami said. “When we order these tests, sometimes we do it through a commercial lab. That commercial lab is not integrated in the EHR most of the time. When the results come, they get scanned and put it in one of the tabs in the EHR, but if there are hundreds of these records, sometimes it becomes hard to find out where they are.”
Partnerships between EHRs and commercial labs have developed over the past few years, and Swami expects more in the future.
Combine those with AI, more data on the benefits of PARP inhibitors — particularly in early-line settings — and laws capping out-of-pocket expenses, and Swami said he expects care to improve in the future.
“I think there will be a big push in terms of integrating next-generation sequencing in decision-making,” he said. “Not only us, but many other investigators are reporting these types of findings.”
Study details
Receipt of PARP Inhibitors in Patients With Metastatic Prostate Cancer Harbouring BRCA1/2 Alterations
Micah Ostrowski, Yeonjung Jo, Chadi Hage Chehade et al
Published in JAMA Network on 2 October 2025
Key Points
Question How often are poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors used in patients with metastatic castration–resistant prostate cancer (mCRPC) harbouring BRCA1/2 alterations?
Findings In this cohort study of 443 patients with mCRPC and BRCA1/2 alterations, 51.2% received a PARP inhibitor, whereas 48.8% did not. Patients with Medicare insurance had higher odds of receiving a PARP inhibitor.
Meaning These findings suggest that despite the availability of biomarker-selected life-prolonging therapies, a sizeable number of patients with mCRPC and BRCA1/2 alterations do not receive PARP inhibitors, highlighting the need to improve awareness of the data and access to these agents.
Abstract
Importance
Patients with metastatic castration–resistant prostate cancer (mCRPC) harbouring 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.
Objective
To investigate the use of PARP inhibitors in patients with mCRPC harbouring BRCA1/2 alterations.
Design, Setting, and Participants
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 harbouring BRCA1/2 alterations and alive after August 15, 2020 (ie, three months after the approval of the first PARP inhibitor, rucaparib, in mCRPC) were included. Statistical analysis was performed from September 2024 to May 2025.
Exposures
Age, race and ethnicity, insurance status, and practice type at the time of mCRPC diagnosis.
Main Outcomes and Measures
The receipt of PARP inhibitors. Multivariable logistic regression was conducted to assess the association between the exposures and the main outcome.
Results
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 centres (odds ratio, 1.64; 95% CI, 1.00-2.70; P = .05).
Conclusions and Relevance
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.
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