PARP Inhibitor Combination Therapy in Metastatic Prostate Cancer
Key Points
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The BRCAAway study demonstrated a significant progression-free survival (PFS) and a landmark overall survival (OS) benefit for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/2 or ATM mutations when treated with abiraterone plus olaparib compared with either agent alone.
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The phase 2 trial findings highlight the importance of early germline and somatic genetic testing to identify patients who may benefit from targeted combination therapy.
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Barriers to the implementation of genetic testing in real-world practice include limited uptake in community settings, delays in acting on results, treatment toxicity, and cost.
Data from the BRCAAway trial reinforce the importance of early and comprehensive genetic testing in prostate cancer to help guide the use of targeted combination therapies that may improve survival. At an event coinciding with the 2026 ASCO Genitourinary Cancers Symposium (ASCO GU 2026), Karan Jatwani, MD, of George Washington Cancer Center, and Jeffrey Zhong, MD, of Case Western Reserve University, discussed the trial’s findings, its treatment implications, and barriers to genetic testing in real-world practice.
The phase 2 trial evaluated abiraterone plus olaparib, abiraterone alone, or olaparib alone in patients with mCRPC who harbor homologous recombination repair gene alterations, such as BRCA1/2 and ATM mutations.
Results presented at ASCO GU 2026 showed that the combination arm reached a median OS of 68 months compared with 28 months for abiraterone alone and 37 months for olaparib alone. At 60 months, the OS rate was 55% for patients treated with abiraterone plus olaparib. The median PFS was 39 months with the combination versus 14 months with olaparib and 8.6 months with abiraterone.
These findings improve understanding of the aggressive biology associated with HRR-mutated prostate cancer and suggest that earlier therapeutic intervention may lead to more meaningful long-term outcomes, Dr. Jatwani said.
However, several barriers remain in real-world practice, he said. These include inconsistent adoption of genetic testing in community settings, delays in acting on test results, treatment-related toxicities like bone marrow suppression with PARP inhibitors, and financial obstacles that may limit patient access.