The U.S. Food and Drug Administration (FDA) approved talazoparib (Talzenna, Pfizer Inc.) in combination with enzalutamide on October 26, 2026, for the treatment of adults with metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer harboring homologous recombination repair (HRR) gene mutations, as detected by an FDA-authorized test.
The approval was supported by data from the TALAPRO-3 trial, in which the combination reduced the risk of radiographic progression or death by 52% compared with enzalutamide plus placebo. Overall survival data were immature at the time of the primary analysis.
Key finding
In TALAPRO-3, talazoparib plus enzalutamide produced a median radiographic progression-free survival that was not reached versus 45.8 months with placebo plus enzalutamide (HR 0.48; 95% CI: 0.36, 0.65; p<0.0001) in patients with HRR gene-mutated mAPMN/S prostate cancer, though overall survival data remain immature.
Study Design
| Trial | TALAPRO-3 (NCT04821622); randomized, double-blind, placebo-controlled |
|---|---|
| Population | 599 adults with HRR gene-mutated mAPMN/S prostate cancer; HRR mutation status confirmed prospectively via tumor tissue or ctDNA-based next-generation sequencing across 12 specified genes (ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C) |
| Treatment | Enzalutamide plus talazoparib 0.5 mg orally once daily vs. enzalutamide plus placebo; all patients received continuous androgen deprivation therapy (GnRH analog or prior bilateral orchiectomy); randomized 1:1 |
| Primary endpoint | Radiographic progression-free survival (rPFS) per RECIST v1.1 and PCWG3 (bone) criteria, assessed by investigator |
| Key secondary endpoints | Overall survival (OS) |
TALAPRO-3 enrolled patients across both androgen pathway modulation-naïve and -sensitive disease settings, with HRR mutation status determined prospectively using either tumor tissue or circulating tumor DNA, reflecting the assay flexibility increasingly seen in biomarker-selected prostate cancer trials. The review was conducted under FDA’s Project Orbis framework in collaboration with the Australian Therapeutic Goods Administration and Health Canada; reviews at those agencies were described as ongoing at the time of FDA approval.
Results and Safety
The primary endpoint was met with high statistical significance: median rPFS was not reached in the talazoparib-plus-enzalutamide arm (95% CI: NR, NR) compared with 45.8 months (95% CI: 37.7, NR) in the placebo-plus-enzalutamide arm, corresponding to a hazard ratio of 0.48 (95% CI: 0.36, 0.65; p<0.0001). OS data were immature at the time of the rPFS analysis; no mature OS results were disclosed.
The FDA’s prescribing information for talazoparib carries warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryo-fetal toxicity. Detailed adverse event rates and discontinuation data from TALAPRO-3 were not included in the FDA’s approval summary and will be available in the full prescribing information posted to Drugs@FDA.
Clinical Context
This approval extends the labeled use of talazoparib beyond its existing indications and adds a PARP inhibitor option to the mAPMN/S prostate cancer setting for patients whose tumors harbor HRR mutations. The companion diagnostic requirement — with FoundationOne CDx and FoundationOne Liquid CDx previously authorized for this purpose — means patient selection depends on prospective molecular testing, reinforcing the role of HRR profiling earlier in the disease course. The application received priority review designation, reflecting the unmet need in this biomarker-defined population.
Whether the rPFS benefit will translate into an overall survival advantage remains to be determined as the TALAPRO-3 OS data continue to mature. The long median rPFS of 45.8 months in the control arm also underscores the need for longer follow-up before the full magnitude of the combination’s benefit can be characterized.
Sources
- U.S. Food and Drug Administration. “FDA Approves Talazoparib + Enzalutamide for Metastatic Androgen Pathway Modulation-Naive or -Sensitive Prostate Cancer.” Drug approval announcement. October 26, 2026. View source.
