New PARP Inhibitor Approved for Breast Cancer
The FDA approval of talazoparib means there are now two PARP inhibitors that can be used to treat patients with breast cancer who have an inherited BRCA mutation.
The U.S. Food and Drug Administration (FDA) recently approved a new molecularly targeted therapeutic called talazoparib (Talzenna) for treating patients with breast cancer that tests positive for a cancer-associated BRCA1 or BRCA2 (BRCA1/2) mutation.
Talazoparib is intended for patients who have metastatic or locally advanced HER2-negative breast cancer and who inherited the BRCA1/2 mutation. At the same time as approving talazoparib for this use, the FDA also approved a genetic test — the BRACAnalysis CDx test — to identify the patients who have inherited BRCA1/2 mutation-positive breast cancer and are eligible to receive talazoparib.
Inherited BRCA1/2 mutations account for between 5 percent and 10 percent of breast cancer cases diagnosed in U.S. women. They also account for a similar proportion of ovarian cancer cases.
Research has shown that blocking the function of proteins called poly ADP-ribose polymerase (PARP) proteins can cause cells with cancer-associated BRCA1/2 mutations to die.
This research has led to the clinical development and FDA approval of several PARP inhibitors as a treatment for patients with cancers harboring inherited BRCA1/2 mutations. Before the approval of talazoparib, three PARP inhibitors had been approved for treating certain women with an inherited BRCA1/2 mutation who have ovarian cancer: olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula). Olaparib had also been approved for treating certain patients with an inherited BRCA1/2 mutation who have metastatic HER2-negative breast cancer.
The approval of talazoparib for patients with inherited BRCA1/2 mutation-positive breast cancer was based on results from the randomized, phase III EMBRACA clinical trial. The results showed that among the 287 patients who received talazoparib, the median time before disease progressed was 8.6 months. This was statistically significantly greater than the 5.6 months median time before disease progressed among the 144 patients who received cytotoxic chemotherapy.
The results that led to the FDA decision were first presented at the 2017 San Antonio Breast Cancer Symposium, which is the world’s leading annual breast cancer meeting that the AACR jointly sponsors with the UT Health San Antonio Cancer Center and Baylor College of Medicine, and later published in the New England Journal of Medicine.
The FDA approval was rendered on Oct. 16, 2018.