The U.S. Food and Drug Administration has approved talazoparib (Talzenna) in combination with enzalutamide for adults with metastatic prostate cancer that has certain homologous recombination repair (HRR) gene mutations. The approval, announced October 26, 2026, applies to cancer that is androgen pathway modulation-naïve or -sensitive—meaning it has not been treated with, or remains sensitive to, treatment targeting the androgen hormone pathway. An FDA-authorized test must identify an eligible mutation.
The approval highlights the importance of biomarker testing: the combination is intended for patients with qualifying gene changes, not everyone with metastatic prostate cancer.fda
What did the study show?
The approval was based on TALAPRO-3, a clinical trial involving 599 patients with HRR gene-mutated metastatic prostate cancer. Participants were randomly assigned to receive enzalutamide with either talazoparib or a placebo. Everyone also received ongoing androgen deprivation therapy, which lowers testosterone.
The study’s main measure was radiographic progression-free survival—the time before cancer worsened on imaging scans or a patient died.
Adding talazoparib reduced the risk of cancer progression or death by 52% compared with enzalutamide alone. Median radiographic progression-free survival was 45.8 months in the placebo-plus-enzalutamide group and had not yet been reached in the talazoparib-plus-enzalutamide group. “Not reached” means too few patients had experienced progression or died to calculate the midpoint at the time of the analysis; it does not mean the cancer will remain controlled indefinitely.
Researchers do not yet know whether the combination helps patients live longer. Overall survival results were not mature enough to draw that conclusion when the progression-free survival analysis was conducted.
Who may qualify?
Patients must have metastatic disease—prostate cancer that has spread to other parts of the body—and an eligible HRR gene mutation detected by an FDA-authorized test. The trial included mutations in genes such as BRCA1, BRCA2, ATM, CDK12 and PALB2, among others. Testing used either tumor tissue or circulating tumor DNA, which consists of DNA fragments from cancer found in the blood.
The FDA has authorized FoundationOne CDx and FoundationOne Liquid CDx as companion diagnostic tests to help identify patients eligible for talazoparib plus enzalutamide. A companion diagnostic is a test used to determine whether a particular treatment may be appropriate.
How is the treatment given?
Talazoparib is taken by mouth once daily with enzalutamide. The FDA-recommended talazoparib dose is 0.5 mg daily, with treatment continued until the cancer progresses or side effects become unacceptable.
The combination does not replace testosterone-lowering treatment. Patients must also receive a gonadotropin-releasing hormone, or GnRH, medicine unless they have already undergone surgery to remove both testicles.
What are the important safety considerations?
Talazoparib’s prescribing information includes warnings about:
- Myelosuppression, or reduced blood cell production.
- Myelodysplastic syndrome and acute myeloid leukemia, serious disorders affecting the bone marrow and blood.
- Potential harm to an unborn baby.
Patients should discuss the combination’s risks, monitoring requirements and potential effects on other medical conditions with their cancer care team.
What does this mean for patients?
For eligible patients, the approval provides a treatment option that delayed cancer progression compared with enzalutamide alone, with both groups continuing testosterone-lowering therapy. It does not yet establish a survival benefit.
Patients with metastatic prostate cancer can ask their oncology team whether they have had testing for HRR gene mutations, whether their results meet the treatment’s eligibility requirements, and how the potential benefit of adding talazoparib compares with its risks.
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