Overview
PARP inhibitors are approved therapies for men with metastatic castration-resistant prostate cancer (mCRPC) that carry specific genetic mutations affecting DNA repair genes. While BRCA mutations are well-known, many other DNA repair gene mutations also exist and may benefit from these same drugs. However, a new real-world study reveals significant gaps in how these patients are being identified and treated.
Using the Flatiron Health Panoramic Database comprised of >370K patients with prostate cancer, researchers analyzed data from nearly 28,000 men diagnosed with mCRPC between 2020 and 2025. They found that just over half underwent genetic testing for DNA repair mutations. Of those tested, 28% had mutations—but surprisingly, 66% had non-BRCA mutations (most commonly in ATM, CHEK2, and CDK12 genes) rather than BRCA mutations. The critical finding: men with non-BRCA mutations were much less likely to receive PARP inhibitors (29% versus 48% with BRCA mutations) despite potentially benefiting from these drugs.
When men with non-BRCA mutations did receive PARP inhibitors, they experienced shorter survival—about 12.3 months compared to 15.2 months for those with BRCA mutations—progressed to the next treatment faster, and received PARPi in later lines.
Why this matters
These findings reveal that many patients with mCRPC with treatable genetic mutations may need PARPi sooner. The study demonstrates the need for broader genetic testing and more equitable access to PARP inhibitors for all patients with DNA repair mutations, not just BRCA carriers, to improve outcomes and care of patients with mCRPC.