New trial results point toward a more targeted approach to metastatic castration-sensitive prostate cancer | ASCO 2026

The combination of PARP inhibitor talazoparib and enzalutamide, which is a hormone-blocking drug, was more effective at treating metastatic castration-sensitive prostate cancer than enzalutamide alone in patients whose tumors carry specific DNA repair gene mutations, according to an abstract presented today at the 2026 annual American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 29 to June 2 in Chicago.

The abstract, called ‘TALAPRO-3: Talazoparib (TALA) + enzalutamide (ENZA) compared with placebo (PBO) + ENZA for the treatment of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations,’ was presented during ‘Genitourinary Cancer — Prostate, Testicular, and Penile,’ by lead author Neeraj Agarwal, M.D., an associate professor of medicine at the Huntsman Cancer Institute, University of Utah.

TALAPRO-3 builds on TALAPRO-2, which studied the effects of this combination on metastatic castration-resistant prostate cancer (mCRPC), which is characterized by the spread of cancer cells beyond the prostate and into the surrounding tissue and organs, driven by testosterone. This specific type of cancer no longer responds to hormone therapy treatments, including androgen deprivation therapy. Approximately half of prostate cancer patients treated with hormone therapy have cancer that becomes treatment-resistant within two to three years. As a result, approximately half of patients will die, as it has a survival rate of approximately 38%, according to the Mayo Clinic.

In patients with metastatic castration-sensitive prostate cancer, cancer cells have also spread outside the prostate but still respond to hormone therapies that lower testosterone.

In TALAPRO-3, Agarwal and his team randomized 599 patients 1:1 to receive either 0.5 mg of talazoparib and 160 mg of enzalutamide once daily or placebo plus 160 mg of enzalutamide once daily. After approximately three years of follow-up, researchers found that patients receiving the combination therapy had a 52% lower risk of cancer progression or death compared to those on enzalutamide alone.

Notably, the median time to progression had not yet been reached in the combination group, while patients on standard treatment progressed at a median of 45.8 months. Among patients with BRCA mutations specifically, the benefit was even more pronounced, with a 63% reduction in risk.

Overall survival data also trended in favor of the combination, with fewer deaths observed in the talazoparib + enzalutamide group (74 versus 91).

The most common treatment adverse effects in patients treated with talazoparib + enzalutamide were anemia (71.2%), fatigue (28.4%) and a decreased neutrophil count (27.1%). Researchers report that these side effects were generally manageable with dose modification, although approximately 1 in 5 patients had to quit the study due to their side effects.

“These results support talazoparib plus enzalutamide as a potential treatment option for patients with HRR gene‑altered metastatic castration‑sensitive prostate cancer, and early molecular testing is critically important now in these patients,” Agarwal concluded during his abstract presentation at ASCO. ““I’m pleased to report that these data are published now in the New England Journal of Medicine.”