General Information

Talzenna (talazoparib) is a poly (ADP-ribose) polymerase (PARP) inhibitor.

Talzenna is specifically indicated for the treatment of adult patients with deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA)-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer.

Talzenna is supplied as a capsule for oral administration. The recommended dose of Talzenna is 1 mg taken orally once daily, with or without food. A 0.25 mg capsule is available for dose reduction. Patients should be treated until disease progression or unacceptable toxicity occurs. The capsule should be swallowed whole and must not be opened or dissolved. If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time.

Mechanism of Action

Talzenna (talazoparib) is an inhibitor of poly (ADP-ribose) polymerase (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 BRCA 1 and 2, 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 human patient-derived xenograft breast cancer tumor models that expressed mutated or wild-type BRCA 1 and 2.

Clinical Trial Results

The FDA approval of Talzenna was based on EMBRACA, an open‑label trial which randomized 431 patients with gBRCAm HER2‑negative locally advanced or metastatic breast cancer. The patients received talazoparib (1 mg) or physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine). All patients were required to have a known deleterious or suspected deleterious gBRCA mutation and must have received no more than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease. Patients were required to have received treatment with an anthracycline and/or a taxane (unless contraindicated) in the neoadjuvant, adjuvant, and/or metastatic treatment setting. The primary efficacy outcome was progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, as assessed by blinded independent central review. Estimated median PFS was 8.6 and 5.6 months in the talazoparib and chemotherapy arms, respectively.