Talazoparib

TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for: Breast Cancer • As a single agent, for the treatment of adult patients with deleterious or suspected deleterious germline BRCA -mutated (g BRCA m) HER2-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-authorized companion diagnostic for TALZENNA. Prostate Cancer In combination with enzalutamide for the treatment of adult patients with: • metastatic androgen pathway modulation-resistant (mAPMR) prostate cancer with homologous recombination repair (HRR) gene mutations, as detected by an FDA-authorized test. • metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer with HRR gene mutations, as detected by an FDA-authorized test.

Talazoparib is an inhibitor of PARP enzymes, including PARP1 and PARP2, which play a role in DNA repair. In vitro studies with cancer cell lines that harbored defects in DNA repair genes, including BRCA1 and BRCA2, have shown that talazoparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, decreased cell proliferation, and apoptosis. Talazoparib anti-tumor activity was observed in patient-derived xenograft breast cancer models bearing mutated BRCA1 or mutated BRCA2 or wild type BRCA1 and BRCA2.

• Breast Cancer • The recommended dosage of TALZENNA is 1 mg orally once daily until disease progression or unacceptable toxicity. • Prostate Cancer • The recommended dosage of TALZENNA is 0.5 mg orally once daily with enzalutamide until disease progression or unacceptable toxicity. • Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had a bilateral orchiectomy. • Take TALZENNA with or without food. • Renal Impairment • Reduce the dose and monitor for increased adverse reactions for patients with moderate or severe renal impairment.

None. None.

• Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): MDS/AML occurred in patients exposed to TALZENNA, and some cases were fatal. Monitor patients for hematological toxicity and discontinue if MDS/AML is confirmed. • Myelosuppression: TALZENNA may affect hematopoiesis and can cause anemia, leukopenia/neutropenia, and/or thrombocytopenia. • Embryo-Fetal Toxicity: TALZENNA can cause fetal harm. Advise of the potential risk to the fetus and to use effective contraception.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Myelodysplastic Syndrome/Acute Myeloid Leukemia • Myelosuppression Most common adverse reactions (≥20%) as a single agent, including laboratory abnormalities, are: • Decreased hemoglobin, decreased neutrophils, decreased lymphocytes, decreased platelets, fatigue, increased glucose, increased aspartate aminotransferase, increased alkaline phosphatase, increased alanine aminotransferase, decreased calcium, nausea, headache, vomiting, alopecia, diarrhea, and decreased appetite. Most common adverse reactions (≥20%) in combination with enzalutamide, including laboratory abnormalities, are: • Decreased hemoglobin, decreased neutrophils, decreased lymphocytes, decreased platelets, fatigue, decreased albumin, decreased calcium, back pain, decreased appetite, and nausea.

• P-gp Inhibitors: Reduce the dose when coadministered with certain P-gp inhibitors. Monitor for increased adverse reactions. • BCRP Inhibitors: Monitor for potential increased adverse reactions.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).