FDA approves talazoparib with enzalutamide for metastatic androgen pathway modulation-naïve or -sensitive prostate cancer with HRR gene mutations
The FDA approved talazoparib (Talzenna) plus enzalutamide on Oct 26, 2026 for adults with metastatic androgen pathway modulation-naïve or -sensitive prostate cancer with HRR gene mutations, as detected by an FDA-authorized test. Approval was supported by the phase 3 TALAPRO-3 trial showing a statistically significant radiographic progression-free survival benefit versus placebo plus enzalutamide (HR 0.48; p<0.0001). Overall survival data were immature at the time of rPFS analysis.
Regulatory approval (FDA)
On Oct 26, 2026, the FDA approved talazoparib (Talzenna; Pfizer) in combination with enzalutamide for adults with metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer with homologous recombination repair (HRR) gene mutations, as detected by an FDA-authorized test.
The FDA previously approved FoundationOne CDx and FoundationOne Liquid CDx as companion diagnostic devices to identify patients with prostate cancer with HRR gene alterations for treatment with talazoparib plus enzalutamide.
Supporting evidence
Efficacy and safety were 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 randomized 1:1 to enzalutamide + talazoparib or enzalutamide + placebo; all patients received continuous androgen deprivation therapy. HRR mutation status (including ATM, ATR, BRCA1/2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C) was prospectively determined using tumor tissue or ctDNA NGS tests.
The primary endpoint was investigator-assessed rPFS (RECIST 1.1 and PCWG3). Median rPFS was not reached with talazoparib/enzalutamide vs 45.8 months with placebo/enzalutamide (HR 0.48, 95% CI 0.36–0.65; p<0.0001). OS data were immature.
Key labeling elements
Warnings/precautions include MDS/AML, myelosuppression, and embryo-fetal toxicity. Recommended talazoparib dose: 0.5 mg orally once daily with enzalutamide until progression or unacceptable toxicity; patients should also receive a GnRH analog or have had bilateral orchiectomy.
The review was conducted under Project Orbis with collaboration from Australia’s TGA and Health Canada; reviews remain ongoing at partner agencies.