publication date: Jan. 12, 2018

Drugs and Targets

FDA expands indications for AZ’s Lynparza, making it first treatment for breast cancer with BRCA mutation

FDA expanded the approved use of Lynparza (olaparib tablets) to include the treatment of patients with certain types of metastatic breast cancer whose tumors have a specific germline mutation.

Lynparza becomes the first PARP inhibitor approved to treat breast cancer. This is also 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 an FDA-approved genetic test, called the BRACAnalysis CDx.

Lynparza is sponsored by AstraZeneca Pharmaceuticals LP. BRACAnalysis CDx is sponsored by Myriad Genetic Laboratories Inc.

“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,” Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “This approval demonstrates the current paradigm of developing drugs that target the underlying genetic causes of a cancer, often across cancer types.”

Lynparza was first approved by the FDA in 2014 to treat certain patients with ovarian cancer and is now indicated for the treatment of patients with BRCA-mutated, HER2-negative metastatic breast cancer, who have been previously treated with chemotherapy. Patients with HR-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine treatment.

In its most recent action, FDA also expanded the approval of the BRACAnalysis CDx, an approved companion diagnostic to Lynparza, 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 based on 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 (progression-free survival). The median progression-free survival for patients taking Lynparza was 7 months compared to 4.2 months for patients taking chemotherapy only.

Common side effects of Lynparza include anemia, neutropenia, leukopenia, nausea, fatigue, vomiting, nasopharyngitis, respiratory tract infection, influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation and inflammation and stomatitis.

Severe side effects of Lynparza include development of myelodysplastic syndrome/acute myeloid leukemia and pneumonitis.

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