Pfizer Wins U.S. Approval for Earlier Prostate Cancer Treatment as Risk of Progression Falls 52%
Key Facts
On October 26, 2026, the U.S. Food and Drug Administration approved talazoparib with enzalutamide to treat adults with metastatic prostate cancer and mutations in homologous recombination repair genes. The indication requires the mutations to be confirmed by an FDA-approved diagnostic test. The targeted condition is metastatic hormone-sensitive disease or disease not previously treated through the androgen pathway. The approval moves the drug combination to an earlier stage of disease than its previous use in hormone therapy-resistant cancer. Pfizer said Phase 3 results showed a 52% reduction in the risk of radiographic disease progression or death compared with enzalutamide plus a placebo.
The agency’s decision was based on the TALAPRO-3 trial, a randomized, double-blind study that compared the combination therapy with enzalutamide plus a placebo. The trial included 599 patients with mutations in homologous recombination repair genes, divided equally between the two treatment groups. All participants received continuous androgen deprivation therapy. Researchers used tumor tissue or circulating tumor DNA to determine mutation status before treatment. The FDA had previously approved the FoundationOne CDx and FoundationOne Liquid CDx tests to identify eligible patients.
In the analysis of radiographic progression-free survival, the median in the talazoparib and enzalutamide group had not been reached and could not be estimated at the time of analysis. The median was 45.8 months among those who received enzalutamide with a placebo. The hazard ratio was estimated at 0.48, with a 95% confidence interval of 0.36 to 0.65 and a probability value of less than 0.0001. This is consistent with the 52% relative reduction in the risk of radiographic disease progression or death reported by Pfizer. However, overall survival data remained immature when the radiographic progression-free survival analysis was conducted, so the agency did not provide a final result for that measure.
Eligibility is limited to patients with confirmed alterations in a list of 12 genes associated with DNA repair. The list includes ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2 and RAD51C. It covers BRCA alterations and other homologous recombination repair gene alterations. In March 2026, Pfizer estimated that these alterations occur in about 25% of metastatic prostate cancer cases. The company linked their presence to a worse prognosis and a lower response to available standard treatments.
Anemia was the most common Grade 3 or higher adverse event in the safety data reported by Pfizer. It was recorded in 51% of patients who received the combination, compared with 3% in the control group. Five percent of patients discontinued talazoparib because of anemia. The FDA recommends a talazoparib dose of 0.5 mg orally once daily with enzalutamide. Treatment continues until disease progression or unacceptable toxicity, with a gonadotropin-releasing hormone analog given concurrently or after bilateral orchiectomy.
The combination received its first U.S. approval in 2023 to treat metastatic castration-resistant prostate cancer in patients with mutations in homologous recombination repair genes. The new approval expands its use to include patients with hormone-sensitive disease or disease not previously treated through this pathway. Before the decision, the global principal investigator of the TALAPRO-3 trial said the combination “extends the time patients can live without their cancer worsening.” In March 2026, Pfizer said an interim analysis showed a trend toward improved overall survival, without announcing that the measure had reached statistical significance at the time. Pfizer shares closed at $30.03 on October 23, 2026, according to L7 data.
The FDA granted the application priority review and conducted the review under Project Orbis in collaboration with Australia’s Therapeutic Goods Administration and Health Canada. The agency said the reviews by both authorities were still ongoing. According to Pfizer, review of the use in hormone-sensitive disease had also extended to the European Medicines Agency. The company said the combination was approved to treat castration-resistant cancer in more than 60 countries, with indications varying from country to country. These regulatory processes outside the United States remain under review or subject to local differences in the scope of approval.