FDA has expanded the approved use of Lynparza (olaparib tablets), from AstraZeneca Pharmaceuticals, Cambridge, UK, to include the treatment of patients with certain types of breast cancer that have spread and whose tumors have a specific inherited genetic mutation, making it the first drug in its class approved to treat breast cancer. The agency’s action marks the first time any drug has been approved to treat certain patients with metastatic breast cancer who have a BRCA gene mutation.

Patients are selected for treatment with Lynparza based on the results of testing with the BRACAnalysis companion diagnostic, an FDA-approved genetic test by Myriad Genetic Laboratories, Salt Lake City.

Richard Pazdur, MD,  FDA.

Richard Pazdur, MD, FDA.

“This class of drugs has been used to treat advanced, BRCA-mutated ovarian cancer, and has now shown efficacy in treating certain types of BRCA-mutated breast cancer,” says Richard Pazdur, MD, director of FDA’s oncology center of excellence and acting director of the Office of Hematology and Oncology Products in the Center for Drug Evaluation and Research. “This approval demonstrates the current paradigm of developing drugs that target the underlying genetic causes of a cancer, often across cancer types.”

Breast cancer is the most common form of cancer in the United States. The National Cancer Institute of the National Institutes of Health estimates approximately 252,710 women will be diagnosed with breast cancer this year, and 40,610 will die of the disease. Approximately 20% to 25% of patients with hereditary breast cancers, and 5% to 10% of patients with any type of breast cancer, have a BRCA mutation. BRCA genes are involved in repairing damaged DNA, and they normally work to prevent tumor development. However, mutations of BRCA genes may lead to certain cancers, including breast cancers.

Lynparza is a poly ADP-ribose polymerase (PARP) inhibitor that blocks an enzyme involved in repairing damaged DNA. When the enzyme is blocked, the DNA inside cancerous cells with damaged BRCA genes may be less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth.

FDA first approved Lynparza in 2014 to treat certain patients with ovarian cancer. The drug is now indicated for the treatment of patients with germline breast cancer susceptibility gene (BRCA)-mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, who have been previously treated with chemotherapy. Patients with hormone receptor-positive breast cancer should have been treated with a prior hormonal (endocrine) therapy, or be considered inappropriate for endocrine treatment.

The BRACAnalysis companion diagnostic from Myriad Genetic Laboratories.

The BRACAnalysis companion diagnostic from Myriad Genetic Laboratories.

FDA also expanded its approval of the BRACAnalysis test to include the detection of BRCA mutations in blood samples from patients with breast cancer.

The safety and efficacy of Lynparza for the treatment of breast cancer was established via a randomized clinical trial of 302 patients with HER2-negative metastatic breast cancer with a germline BRCA mutation. The trial measured the length of time the tumors did not have significant growth after treatment. The median progression-free survival for patients taking Lynparza was 7 months, compared to 4.2 months for patients receiving only chemotherapy.

FDA granted the application priority review after determining that the drug would significantly improve the safety or effectiveness of treating, diagnosing, or preventing a serious condition.

Lynparza is also approved for the treatment of patients with BRCA-mutated, advanced ovarian cancer who have received three or more treatments of chemotherapy; and for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, whose tumors have completely or partially responded to chemotherapy.