FDA Approves Talazoparib for Germline BRCA-Mutated HER2-Negative Breast Cancer
Posted: Thursday, October 18, 2018
On October 16, 2018, the U.S. Food and Drug Administration (FDA) approved the PARP inhibitor talazoparib (Talzenna) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated, 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 the EMBRACA trial (ClinicalTrials.gov identifier NCT01945775), an open‑label trial that randomly assigned 431 patients with germline BRCA-mutated HER2‑negative locally advanced or metastatic breast cancer to receive talazoparib or physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine). All patients were required to have a known deleterious or suspected deleterious germline BRCA-mutated mutation and must have received no more than three prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease. Estimated median progression-free survival was 8.6 and 5.6 months in the talazoparib and chemotherapy arms, respectively.
The prescribing information includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia, myelosuppression, and embryofetal toxicity. Most common (≥ 20%) adverse reactions of any grade were fatigue, anemia, nausea, neutropenia, headache, thrombocytopenia, vomiting, alopecia, diarrhea, and decreased appetite.
The FDA also approved the BRACAnalysis CDx test to identify patients with breast cancer with deleterious or suspected deleterious germline BRCA-mutated 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 germline BRCA-mutation status was confirmed with either prospective or retrospective testing with BRACAnalysis CDx.
