FDA approves talazoparib plus enzalutamide earlier in metastatic prostate cancer with HRR gene mutations

The US Food and Drug Administration on 26 October 2026 expanded the approval of talazoparib (Talzenna) in combination with enzalutamide (Xtandi), Pfizer announced. The combination can now be used in men with metastatic prostate cancer that is still sensitive to hormone therapy (androgen pathway modulation-naïve or -sensitive, also called mHSPC) and that has homologous recombination repair (HRR) gene mutations, including BRCA and non-BRCA mutations, detected by an FDA-authorised test.

Previously, since 2023, the combination was approved in the US only for HRR-mutated castration-resistant disease, a later stage. Pfizer says about 25% of patients with mHSPC have HRR mutations.

The evidence: TALAPRO-3

• Design: randomised, double-blind, placebo-controlled phase 3 trial in 599 patients; talazoparib 0.5 mg/day plus enzalutamide versus placebo plus enzalutamide.
• Result: the combination reduced the risk of radiographic progression or death by 52% (hazard ratio 0.48). Pfizer estimates that about 77% of patients on the combination were progression-free at three years.
• The results were presented at ASCO 2026 and published in The New England Journal of Medicine.

Limitations and safety

• The approval rests on progression-free survival; overall survival is still a secondary endpoint not yet reported, according to Pfizer.
• Side effects were substantial: grade 3 or higher anaemia occurred in 51% of patients on the combination versus 3% in the control group, and 5% stopped talazoparib because of anaemia. Labelling also warns of rare MDS/AML blood cancers with talazoparib.
• Much of this information comes from the manufacturer’s press release.

Whether this treatment is suitable depends on genetic testing and individual factors; talk to your oncologist.