Talzenna Plus Xtandi: A Targeted Option for Some Men With Advanced Prostate Cancer
- On Oct. 26, 2026, the FDA approved talazoparib (Talzenna) plus enzalutamide (Xtandi). It’s for men whose prostate cancer has spread but still responds to hormone therapy, and whose cancer has changes in certain DNA-repair genes.
- In the main study, the combination kept cancer in check on scans longer than enzalutamide alone, but it’s still too early to know whether it helps men live longer.
- Side effects were more common with the combination, especially anemia (low red blood cells). About 4 in 10 men on it needed a blood transfusion.
- You need a genetic test of your tumor or blood to know if you qualify. Ask your care team about testing early.
On Oct. 26, 2026, the U.S. Food and Drug Administration (FDA) approved talazoparib (brand name Talzenna) to be taken together with enzalutamide (sold as Xtandi). It’s for adults with metastatic prostate cancer, meaning it has spread beyond the prostate to places like the bones or lymph nodes. The cancer must also carry changes in specific genes, as shown by an FDA-approved test.
Read MoreWhat ‘Hormone-Sensitive’ Means
Prostate cancer usually needs male hormones, called androgens, to grow. Testosterone is the main one.
That’s why the first treatment for advanced prostate cancer is usually androgen deprivation therapy, or ADT. ADT is medicine (usually shots) or surgery to remove the testicles. Both lower testosterone and starve the cancer of fuel.
When ADT is still keeping the cancer under control, doctors call it hormone-sensitive (you may also hear “castration-sensitive”). The FDA uses a newer label, “androgen pathway modulation-sensitive,” which means the same thing in practice. This stage is often right after diagnosis.
Before now, this combination was only approved for men whose cancer had stopped responding to hormone therapy. Doctors call that stage castration-resistant. Many men with hormone-sensitive disease already get ADT plus a second hormone-blocking pill like enzalutamide. The new approval adds a third drug for men with the right gene changes.
The Gene Changes That Matter
Your cells have built-in tools to fix damaged DNA. One set of these tools is controlled by homologous recombination repair genes, or HRR genes. Two of them may sound familiar: BRCA1 and BRCA2, the same genes linked to breast and ovarian cancer.
When HRR genes are altered, cancer cells lose some of their ability to repair themselves. The study tested for changes in 12 HRR genes.
Why does this matter to you? According to the study, about 29% of men with this type of prostate cancer have HRR gene changes. Those changes have been linked to worse outcomes. They also open the door to a targeted treatment.
“Talazoparib plus enzalutamide is now the only approved PARP inhibitor combination in this setting that includes patients with both BRCA and non-BRCA homologous recombination repair (HRR) gene mutations, expanding access to treatment that targets a weakness in the cancer’s ability to repair DNA,” Dr. Barata says.
That’s an important distinction. Another PARP inhibitor combination, niraparib and abiraterone (brand name Akeega), was approved in December 2025 for this stage of prostate cancer, but only for men with BRCA2 changes. epocrates
How Talazoparib Works
Talazoparib is a PARP inhibitor. PARP is another protein cancer cells use to fix DNA damage.
Cancer cells with HRR gene changes already lean heavily on PARP to survive. Blocking PARP too leaves those cells without ways to repair themselves, and they die. Healthy cells, which still have working repair genes, cope better.
Enzalutamide blocks testosterone’s signal inside the cancer cell. Together, the two drugs hit the cancer from two directions.
What the Study Found
The approval is based on a large study called TALAPRO-3, published in The New England Journal of Medicine and paid for by Pfizer, which makes talazoparib.
It was a phase 3, double-blind trial. That means it compared treatments in a large group, and neither the patients nor their doctors knew who got which. The 599 men were split into two groups. One took talazoparib plus enzalutamide. The other took a placebo (a look-alike pill with no active drug) plus enzalutamide. Everyone stayed on ADT.
The main goal was progression-free survival: how long men lived without their cancer growing or spreading on scans. It shows how long a treatment keeps the cancer in check.
At three years, 77% of men on the combination had no cancer growth on scans. For men on enzalutamide alone, it was 56%.
“In TALAPRO-3, adding talazoparib to enzalutamide and androgen deprivation therapy (ADT) reduced the risk of progression or death by 52% compared with enzalutamide and ADT alone,” Dr. Barata says. “For patients, that offers hope of keeping their cancer controlled longer, although longer follow-up is needed to establish whether patients live longer.”
The benefit showed up in men with BRCA changes and in men with other HRR gene changes. The researchers caution that these smaller group-by-group comparisons are less reliable than the main result.
What We Don’t Know Yet
The big question is whether this combination helps men live longer.
Overall survival is how many men are alive, whatever happened with their cancer. At three years, it was 78% with the combination and 72% with enzalutamide alone. That difference wasn’t large enough to be statistically meaningful at this early check-in. The FDA calls the survival data “immature.” The study is still following patients.
Two other gaps:
- The study didn’t compare this combination with chemotherapy (docetaxel), which some men receive. How the two compare is unknown.
- Fewer than 2% of the men in the study were Black, even though Black men are hit hard by prostate cancer.
Side Effects
The benefit is real, but so are the trade-offs.
The most common side effects with the combination were anemia, tiredness, and low neutrophils, a type of white blood cell that fights infection.
Anemia means too few red blood cells, which carry oxygen through your body. It can leave you tired, short of breath, or dizzy.
- Half the men on the combination developed severe anemia, usually in the first few months.
- About 40% needed at least one blood transfusion.
- Doctors mostly managed anemia by pausing the drug and lowering the dose. Only 5% of men stopped talazoparib because of it.
Serious side effects occurred in 42% of men on the combination, compared with 32% on enzalutamide alone.
Rarer problems were also seen. Three men on the combination developed myelodysplastic syndrome (MDS), a condition where the bone marrow doesn’t make healthy blood cells. Two developed acute myeloid leukemia (AML), a blood cancer. One man on enzalutamide alone developed MDS. Two deaths were considered related to the combination. The FDA label carries warnings about MDS/AML and low blood counts.
If you start this treatment, expect regular blood tests, especially early on. Call your care team if you feel unusually tired or short of breath, or if you get fevers or infections.
How to Find Out if This Applies to You
The only way to know if this treatment fits you is genetic testing of your cancer.
The FDA has approved two tests. One looks at tumor tissue, often from an earlier biopsy. The other is a liquid biopsy, a blood test for circulating tumor DNA, or ctDNA, which is small pieces of cancer DNA floating in your blood. It can help when a tissue sample isn’t available.
“Building on the combination’s established role in castration-resistant disease, this approval moves a biomarker-directed approach earlier when the disease is sensitive to ADT,” Dr. Barata says. “It changes how we select initial therapy for eligible patients and reinforces a critical message: comprehensive genetic testing should happen early, so patients can benefit from these advances when treatment decisions are being made.”
A biomarker is a measurable feature of your cancer, like a gene change, that helps guide treatment.
Questions to Ask Your Doctor
- Has my cancer been tested for HRR or BRCA gene changes? If not, can it be?
- If I have one of these changes, is talazoparib plus enzalutamide right for me?
- How does it compare with other options, like chemotherapy?
- How often will my blood be checked, and what symptoms should I call about?
- Should my family members consider genetic counseling?
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