U.S. FDA Agrees to Review Talazoparib for Advanced and Triple Negative Breast Cancer for Treatment of Patients with an Inherited BRCA Mutation

The U.S. Food and Drug Administration accepted for filing and granted Priority Review designation for Pfizer’s New Drug Application for talazoparib. The submission is based on results from the EMBRACA trial, which compared talazoparib to chemotherapy in patients with inherited BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer.

About Talazoparib

Talazoparib is an investigational anti-cancer medicine called a PARP (poly ADP ribose polymerase) inhibitor. Preclinical studies suggest that talazoparib is highly potent and has a dual mechanism of action, with the potential to induce tumor cell death by blocking PARP enzyme activity and trapping PARP on the sites of DNA damage. Talazoparib has not yet been approved by any regulatory authorities for the treatment of any disease and is only available in clinical trials.

The EMBRACA clinical trial directly compared once-daily talazoparib to chemotherapy in 431 patients with an inherited BRCA1/2 mutation and locally advanced or metastatic triple negative or hormone receptor-positive (HR+)/HER2- breast cancer. According to Pfizer the study met its primary endpoint, demonstrating that talazoparib delayed the time to cancer recurrence and prolonged survival compared to chemotherapy across all prespecified subgroups, including those with triple negative breast cancer, brain metastases, and those with HR+ disease.

About Germline (Inherited) BRCA-Mutated Breast Cancer

BRCA1 and BRCA2 are human genes that produce proteins involved in DNA repair. When either of these genes is altered or mutated, DNA repair may not progress correctly. This can lead to the development of certain types of cancer such as breast cancer.1,2,3 BRCA mutations can be hereditary (germline) or occur spontaneously (somatic).1 Together, BRCA1 and BRCA2 mutations account for about 25 to 30 percent of hereditary breast cancers and about 5 to 10 percent of all breast cancers.4,5

References:

1 National Cancer Institute. BRCA mutations: Cancer risk and genetic testing. https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet. Accessed April 30, 2018.

2 Evers B, Schut E, van der Burg E, et al. A high throughput pharmaceutical screen identifies compounds with specific toxicity against BRCA2-deficient tumors. Clin Cancer Res. 2010 Jan 1; 16(1): 99–108.

3 Livraghi L, Garber J. PARP inhibitors in the management of breast cancer: Current data and future prospects. BMC Medicine. 2015;13:188.

4 Kleibl Z, Kristensen VN. Women at high risk of breast cancer: molecular characteristics, clinical presentation and management. The Breast. 2016;28:136-144.

5 Arpino G, Pensabene M, Condello C, et al. Tumor characteristics and prognosis in familial breast cancer. BMC Cancer. 2016;16(1):924.

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