Talzenna
Deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer, as detected by an FDA-approved test; Metastatic castration-resistant prostate cancer (mCRPC) with HRR gene mutations, in combination with enzalutamide.
Breast cancer: 1 mg orally once daily
Prostate cancer: 0.5 mg orally once daily (with enzalutamide 160 mg daily)
Take with or without food. Swallow capsules whole.
Dose reductions (breast): 0.75 mg → 0.5 mg → 0.25 mg
Renal (CrCl 30-59): 0.75 mg daily (breast), 0.35 mg daily (prostate)
Capsules: 0.25 mg, 1 mg
None listed.
- Myelosuppression: Grade 3-4 anemia (39%), neutropenia (21%), thrombocytopenia (15%). Monitor CBC monthly. Dose reduce, hold, or D/C per severity.
- Myelodysplastic Syndrome/Acute Myeloid Leukemia: MDS/AML in 0.5%. Monitor CBC.
- Embryo-Fetal Toxicity: Can cause fetal harm. Effective contraception required during and 7 months after.
Fatigue (62%), anemia (53%), nausea (49%), neutropenia (35%), headache (33%), thrombocytopenia (27%), vomiting (25%), alopecia (25%), diarrhea (22%), decreased appetite (21%), abdominal pain (19%)
Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.
Talazoparib inhibits poly(ADP-ribose) polymerase (PARP) enzymes, including PARP1 and PARP2, which are involved in DNA damage repair. Talazoparib is the most potent PARP trapper among approved PARP inhibitors — it not only inhibits PARP enzymatic activity (catalytic inhibition) but also stabilizes PARP-DNA complexes (PARP trapping), preventing DNA repair, replication fork progression, and causing cell death. Cancer cells with BRCA1/2 mutations or other HRR deficiencies are especially dependent on PARP for DNA repair, creating synthetic lethality when PARP is inhibited.
Tmax: 1-2 hours. Half-life: approximately 90 hours (long). Protein binding: 74%. Minimally metabolized (no significant CYP involvement). Excreted in urine (69%, 55% unchanged) and feces (20%). P-gp substrate. Steady-state by Week 3.
Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.
- EMBRACA — Talazoparib vs. physician's choice in germline BRCA-mutated HER2- metastatic breast cancer. Phase III, n=431.