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Selected DNA-repair mutations, both germline and somatic, occur in up to 30% of men with metastatic castration-resistant prostate cancer (mCRPC) and appear to be associated with aggressive clinical behavior. Among the most well-characterized genes are BRCA1, BRCA2, and ATM, which lead to increased sensitivity to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition.
Now, investigators have conducted an industry-sponsored, randomized, open-label, phase III trial of the PARP inhibitor olaparib in 387 eligible mCRPC patients with disease progression on either enzalutamide or abiraterone (docetaxel was permitted) and known alterations in 15 genes that have direct or indirect roles in homologous recombination repair. Patients were divid…