Brand: Talzenna

Initial US Approval

  • 2018. HRR gene-mutated mCRPC with enzalutamide: June 20, 2023. Label updated June 2025 with final overall survival data.1,5,6

Indications

HRR Gene-Mutated mCRPC:

  • In combination with enzalutamide for adult patients with HRR gene-mutated metastatic castration-resistant prostate cancer. After an 8 to 0 ODAC vote in May 2025, the FDA did not extend the indication to patients without HRR gene mutations.1,6
  • Patient selection: alterations in ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C. FoundationOne CDx (tissue) and FoundationOne Liquid CDx (blood) were approved as companion diagnostics on June 1, 2026.

Recommended Dose/Route

  • 0.5 mg orally once daily with enzalutamide 160 mg once daily, with or without food, until disease progression or unacceptable toxicity (the breast cancer dose is 1 mg). Patients should also receive a GnRH analog concurrently or should have had bilateral orchiectomy.1

Dose Reductions for Adverse Reactions

Figure

Pivotal Study

TALAPRO-2 (NCT03395197)

  • Key Inclusion Criteria: first-line mCRPC, ECOG 0 or 1; prior CYP17 inhibitor or docetaxel for castration-sensitive disease allowed. Label population: 399 patients with HRR gene mutations (BRCA2 34%, ATM 22%, CDK12 19%, CHEK2 18%, BRCA1 6%).1,3
  • Treatment: randomized 1:1, double blind, talazoparib 0.5 mg plus enzalutamide 160 mg (n=200) vs placebo plus enzalutamide (n=199).1
Figure
  • Fair balance: benefit was greatest in BRCA-mutated disease; in the exploratory non-BRCA HRR subgroup, the rPFS confidence interval crossed 1 and the OS interval reached 1.00. Label rPFS is from the primary analysis and OS from the final analysis.1,4

Safety

TALAPRO-2, HRR-Mutated (N=197)

  • Summary: serious adverse reactions 30%, fatal 1.5%, discontinuation 10%, dose reduction 52% (anemia 43%), dose interruption 58%.1
  • Key warnings: myelodysplastic syndrome/acute myeloid leukemia (0.4%); myelosuppression (among all 511 talazoparib-treated patients, grade 3 or higher anemia 48%, neutropenia 19%, thrombocytopenia 9%; red blood cell transfusion 42%); embryo-fetal toxicity. Monitor blood counts monthly.1
Figure

References

  1. Talzenna (talazoparib) capsules. Prescribing information. Pfizer Inc; revised 06/2025. Accessed October 2026.
  2. Agarwal N, Azad AA, Carles J, et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023;402(10398):291-303. doi:10.1016/S0140-6736(23)01055-3
  3. Fizazi K, Azad AA, Matsubara N, et al. First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: the phase 3 TALAPRO-2 trial. Nat Med. 2024;30(1):257-264. doi:10.1038/s41591-023-02704-x
  4. Fizazi K, Azad AA, Matsubara N, et al. Talazoparib plus enzalutamide in men with HRR-deficient metastatic castration-resistant prostate cancer: final overall survival results from the randomised, placebo-controlled, phase 3 TALAPRO-2 trial. Lancet. 2025;406(10502):461-474. doi:10.1016/S0140-6736(25)00683-X
  5. FDA approves talazoparib with enzalutamide for HRR gene-mutated metastatic castration-resistant prostate cancer. US Food and Drug Administration. June 20, 2023.
  6. US Food and Drug Administration. Oncologic Drugs Advisory Committee meeting, May 21, 2025: talazoparib in combination with enzalutamide. Accessed October 2026.