FDA approves Talzenna for patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative locally advanced or metastatic breast cancer.- Pfizer

The FDA has approved Talzenna (talazoparib), a poly (ADP-ribose) polymerase (PARP) inhibitor, for patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative locally advanced or metastatic breast cancer. Patients must be selected for therapy based on an FDA-approved companion diagnostic for talazoparib.

Approval was based on EMBRACA (NCT01945775), an open-label trial randomizing 431 patients (2:1) with gBRCAm HER2-negative locally advanced or metastatic breast cancer to receive 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 (HR 0.54; 95% CI: 0.41, 0.71; p<0.0001).>

FDA also approved the BRACAnalysis CDx test, from Myriad Genetics, to identify patients with breast cancer with deleterious or suspected deleterious gBRCAm who are eligible for talazoparib. The effectiveness of the BRACAnalysis CDx test was based on the EMBRACA trial population for whom deleterious or suspected deleterious gBRCAm status was confirmed with either prospective or retrospective testing with BRACAnalysis CDx.

Comment: Breast cancer is the first indication for Talzenna, although it is also in Phase III for prostate cancer in combination with Xtandi or Johnson & Johnson's Zytiga. Pfizer�s expansion plans for talazoparib include early triple-negative breast cancer and DNA damage repair-deficient prostate cancer, as well as combination use with its PD-L1 inhibitor Bavencio.