On October 26, 2026, the U.S. Food and Drug Administration (FDA) approved talazoparib (Talzenna, Pfizer) in combination with enzalutamide (Xtandi, Astellas and Pfizer) for metastatic prostate cancer that:
Has not been treated with hormone therapy or hormone therapy still controls the cancer (hormone-sensitive prostate cancer)
Has homologous recombination repair (HRR) gene mutations, as found on an FDA-approved test
Metastatic means that the cancer has spread to other parts of the body.
This drug combination was previously approved in 2023 to treat more advanced metastatic prostate cancer with HRR mutations that could no longer be treated with hormone therapy.
About 1 in 5 people diagnosed with metastatic prostate cancer have HRR mutations. HRR mutations include BRCA2, ATM, CHEK2, BRCA1, and RAD51D. Patients with these mutations are at a higher risk of developing resistance to hormone therapy and have a higher risk of death than patients without them. This expanded approval gives these patients a new treatment option at an earlier stage of the disease: before it becomes resistant to hormone therapy.
“This approval represents a critical advancement for patients with newly diagnosed metastatic prostate cancer with HRR gene mutations, who face a more aggressive disease, worse prognosis, and limited treatment options,” said Dr. Neeraj Agarwal in a press release about the approval. “In the TALAPRO-3 trial, clinical benefits were consistent for patients with BRCA and non-BRCA HRR gene mutations, addressing a long-standing unmet need–and reinforcing the importance of biomarker testing at the time of diagnosis.”
Dr. Agarwal is an oncologist at Dana-Farber Cancer Institute, co-director of the Prostate Cancer Program at Harvard Cancer Consortium, and global lead investigator for TALAPRO-3, the clinical trial that led to the approval of this combination.
What is talazoparib? How do talazoparib and enzalutamide treat prostate cancer?
Talazoparib is a type of targeted therapy called a PARP inhibitor. PARP refers to an enzyme called poly ADP-ribose polymerase. PARP inhibitors block this enzyme, which helps repair DNA inside cancer cells. This stops cancer cells from growing and destroys them.
Enzalutamide is a type of hormone therapy. It helps stop prostate cancer growth by blocking androgen hormones like testosterone.
Both talazoparib and enzalutamide are oral medications. Treatment with this combination continues until the cancer progresses or unacceptable side effects.
TALAPRO-3: The study that led to talazoparib approval
The expanded approval of talazoparib with enzalutamide was based on the phase 3 TALAPRO-3 clinical trial (NCT04821622). It included 599 patients with metastatic HRR-mutated prostate cancer who had received three months or less of androgen deprivation therapy. Patients were randomly assigned to receive a combination of talazoparib with enzalutamide or a placebo with enzalutamide.
During this trial, researchers found:
Talazoparib with enzalutamide reduced the risk of disease progression or death by 52% compared to a placebo with enzalutamide
77% of patients treated with talazoparib with enzalutamide remained progression-free at three years
What are the common side effects of talazoparib with enzalutamide?
The most common side effects of talazoparib with enzalutamide for people with hormone-sensitive metastatic prostate cancer with HRR mutations were:
Anemia
Fatigue
Low neutrophil count (neutropenia)
Weakness
The most common severe side effect was anemia, with 5% of patients stopping treatment with talazoparib due to anemia.
Risk of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) with talazoparib
Talazoparib does include a warning for a higher risk of developing blood cancer. Of 1,096 patients, around 1% developed MDS/AML. Talazoparib should not be given until blood counts have recovered after chemotherapy. Blood counts should be monitored monthly during treatment with talazoparib.
Questions to ask your care team about talazoparib with enzalutamide
If you or a loved one have been recently diagnosed with metastatic HRR-mutated prostate cancer, talk to your care team about this new approval. Consider asking your care team the following questions about talazoparib:
Was I tested for HRR mutations with an FDA-approved test?
Am I eligible for treatment with talazoparib with enzalutamide?
Am I at a higher risk of any severe side effects with talazoparib?
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