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The combination of enzalutamide and talazoparib is a treatment for metastatic castration-resistant prostate cancer (mCRPC) specifically in patients whose cancer has alterations in homologous recombination repair (HRR) genes. Enzalutamide (brand name Xtandi) is an androgen receptor inhibitor that blocks hormones fueling cancer cell growth. Talazoparib (brand name Talzenna) is a PARP inhibitor that blocks DNA repair activities, making cancer cells with altered DNA repair genes harder to survive. In the TALAPRO-2 trial, the combination showed significant benefits compared to enzalutamide alone in patients with HRR gene mutations, including improved overall survival (median 45.8 months vs 37.0 months, 20.4% risk reduction), improved radiographic progression-free survival (33.1 months vs 19.5 months), increased time to cytotoxic chemotherapy, improved time before changing to a new cancer medicine, and a higher rate of tumor reduction (62% vs 44%). The benefit in overall survival was particularly pronounced in the HRR-deficient population (14-month gain, 38% lower risk of death). The most common side effects are anemia (66%, 49% grade 3/4), neutropenia (36%, 19.3% grade 3/4), and fatigue (34%). These side effects frequently led to dose modifications or discontinuation of talazoparib.
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