Phase 3 TALAPRO-2 clinical trial shows that combining the PARP inhibitor talazoparib with the standard hormone therapy enzalutamide significantly improves survival in men with metastatic castration-resistant prostate cancer (mCRPC), a form of the disease that no longer responds to traditional hormone therapy and has spread to other parts of the body.

TALAPRO-2 enrolled men with mCRPC who had not yet received any life-prolonging treatment for this advanced stage of cancer. In a forward-thinking design, the trial included an “all-comers” population, meaning patients were eligible regardless of whether their tumors had mutations in homologous recombination repair (HRR) genes, such as BRCA1, BRCA2 or ATM. Participants were randomly assigned to receive either talazoparib combined with enzalutamide or a placebo with enzalutamide. The primary goal was to determine how long patients lived without their cancer worsening, and earlier results had already shown the combination significantly delayed disease progression. The newly released data now confirm that the combination also helps patients live longer overall.

With a median follow-up of more than 52 months, researchers found that patients treated with talazoparib and enzalutamide had a median overall survival of 45.8 months, compared to 37.0 months for those treated with enzalutamide and placebo. This difference, which met the rigorous threshold for statistical significance (P=0.0155), reflects roughly a 20 percent reduction in the risk of death for patients receiving the combination therapy. The trial also confirmed continued benefit in delaying disease progression, with a median radiographic progression-free survival of 33.1 months in the talazoparib group versus 19.5 months in the control group.

Although the survival advantage was seen in the overall population, the benefit was even more pronounced in men whose tumors had mutations in HRR genes. In this subgroup, the hazard ratio for overall survival was 0.549, suggesting nearly a 50 percent lower risk of death compared to enzalutamide alone. Exploratory analyses indicated that men without HRR or BRCA1/2 alterations might also benefit, although results in these smaller groups were more variable.

No new safety concerns emerged with longer follow-up. The most common serious side effects observed with the combination therapy were anemia, affecting 49 percent of patients, and neutropenia, occurring in 19 percent. While about 22 percent of patients discontinued talazoparib due to side effects, the overall safety profile remained consistent with earlier findings and was considered manageable.

The final results of the TALAPRO-2 trial represent a significant step forward in treating advanced prostate cancer.

Source.