Talazoparib — Drug Monograph

Brand names: Talzenna

Drug class: PARP Inhibitor

Mechanism of Action

Potent inhibitor of PARP1 and PARP2 with the highest PARP-trapping activity among approved PARP inhibitors. PARP trapping — the physical immobilization of PARP protein at DNA single-strand breaks — is thought to be the primary cytotoxic mechanism, rather than catalytic inhibition of PARP enzymatic activity alone. Because talazoparib is a more potent PARP trap than olaparib or niraparib on a per-molecule basis, it can achieve equivalent biological effect at lower concentrations, which also means higher risk of myelosuppression (particularly anemia). In BRCA1/2-mutated cancer cells, the…

FDA Indications

• Germline BRCA1/2-mutated HER2-negative locally advanced or metastatic breast cancer — any line (EMBRACA trial: ORR 62.6% vs. 27.2%, PFS 8.6 vs. 5.6 months vs. physician's choice chemotherapy)
• Germline or somatic BRCA1/2-mutated metastatic castration-resistant prostate cancer (mCRPC) — in combination with enzalutamide (TALAPRO-2 trial)

Common Side Effects

• Anemia (most prominent; more frequent and severe than with olaparib — related to high PARP-trapping potency)
• Fatigue
• Neutropenia
• Thrombocytopenia
• Nausea
• Alopecia (distinguishing toxicity from olaparib and niraparib — relatively uncommon with other PARP inhibitors)
• Headache
• Vomiting
• Decreased appetite

Clinical Pearl

Talazoparib is the preferred PARP inhibitor for BRCA-mutated breast cancer — the EMBRACA trial showed ORR nearly double that of chemotherapy. Alopecia is an important distinguishing toxicity from other PARP inhibitors: talazoparib causes hair loss in roughly 25% of patients, which is uncommon with olaparib or niraparib and is important to counsel patients about before starting. Anemia management is critical — grade 3–4 anemia occurs in ~35% of patients; dose reduction (to 0.75 mg or 0.5 mg) is…

Related Therapies & Mechanisms

• Olaparib (Lynparza) — PARP Inhibitor · Breast
• Rucaparib (Rubraca) — PARP Inhibitor · Prostate
• Docetaxel (Taxotere) — Breast
• Goserelin (Zoladex) — Breast