The Food and Drug Administration approved talazoparib (Talzenna, Pfizer) in combination with enzalutamide on October 26, 2026 for adults with metastatic androgen pathway modulation naive or sensitive prostate cancer with homologous recombination repair gene mutations, as detected by an FDA authorised test. The combination was first cleared in 2023 for castration resistant disease, and the new decision moves it into an earlier treatment setting.
Efficacy rests on TALAPRO-3, a randomised, double blind, placebo controlled trial in 599 patients with HRR gene mutated disease, assigned to enzalutamide plus either talazoparib or placebo, with continuous androgen deprivation therapy. Median investigator assessed radiographic progression free survival was not reached in the talazoparib arm and was 45.8 months in the control arm, a hazard ratio of 0.48 (95 percent confidence interval 0.36 to 0.65, p below 0.0001). At three years, 77 percent of patients on the combination were alive without radiographic progression against 56 percent on enzalutamide alone, according to reporting of the trial.
The limits are part of the decision. Overall survival data were immature at the time of the progression analysis, and it is not yet known whether the trial will meet its survival endpoint. Because the treatment arm has not reached its median, the absolute size of the benefit is not yet defined, and the 45.8 month control median shows enzalutamide alone already provides prolonged disease control in this population. Trade reporting of the trial put grade 3 or higher anaemia at 51 percent on the combination against 3 percent on control.
The recommended talazoparib dose is 0.5 mg orally once daily with enzalutamide, continued until disease progression or unacceptable toxicity, alongside a gonadotropin releasing hormone analogue or prior bilateral orchidectomy. The review was conducted under Project Orbis, and a parallel application is under review at the European Medicines Agency. Eligibility depends on a positive HRR test, with FoundationOne CDx and FoundationOne Liquid CDx previously approved as companion diagnostics for the combination.