FDA Approves Pfizer's Talzenna Plus Enzalutamide for HRR-Mutated Metastatic Prostate Cancer

On October 26, 2026, the FDA approved talazoparib (Talzenna, Pfizer) in combination with enzalutamide for adults with metastatic androgen pathway modulation-naive or -sensitive (mAPMN/S) prostate cancer with homologous recombination repair (HRR) gene mutations, as detected by an FDA-authorized test.

The FDA had previously approved the FoundationOne CDx and FoundationOne Liquid CDx assays as companion diagnostics to identify patients with prostate cancer with HRR gene alterations for treatment with the combination. The application received Priority review and was reviewed under Project Orbis, with the FDA collaborating with the Australian Therapeutic Goods Administration and Health Canada; reviews at those agencies are ongoing.

Efficacy was evaluated in TALAPRO-3 (NCT04821622), a randomized, double-blind, placebo-controlled trial in which 599 patients with HRR gene-mutated mAPMN/S prostate cancer were assigned 1:1 to enzalutamide plus either talazoparib or placebo daily. All patients also received continuous androgen deprivation therapy. Mutation status in 12 HRR genes, including BRCA1, BRCA2, ATM, and CDK12, was determined prospectively with tumor tissue or circulating tumor DNA-based next-generation sequencing. The major efficacy outcome was investigator-assessed radiographic progression-free survival (rPFS). Median rPFS was not reached in the talazoparib arm vs 45.8 months in the placebo arm (hazard ratio, 0.48; 95% CI, 0.36-0.65).

Overall survival, an additional efficacy outcome, was immature at the time of the rPFS analysis. The prescribing information includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity.

The recommended talazoparib dosage is 0.5mg orally once daily with enzalutamide until disease progression or unacceptable toxicity; the FDA refers to the enzalutamide prescribing information for enzalutamide dosing. Patients should also receive a gonadotropin-releasing hormone analog concurrently or have had a bilateral orchiectomy, according to the agency.

Source: US Food and Drug Administration. FDA approves talazoparib with enzalutamide for metastatic androgen pathway modulation-naïve or -sensitive prostate cancer with HRR gene mutations. US Food and Drug Administration; October 26, 2026. Accessed October 26, 2026.