FDA Approves First Drug for BRCA-Mutated Breast Cancer

Today, the FDA approved olaparib tablets (Lynparza) for the treatment of patients with metastatic breast cancer whose tumors have a germline genetic mutation, according to a press release.

The expanded approval makes olaparib the first PARP inhibitor indicated for breast cancer, in addition to being the first drug approved to treat patients with a BRCA mutation.

Patients may receive treatment with olaparib tablets after undergoing the genetic test BRACAnalysis CDx, according to the release.

“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,” said Richard Pazdur, MD, director of the FDA 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. “This approval demonstrates the current paradigm of developing drugs that target the underlying genetic causes of a cancer, often across cancer types.”

Although BRCA genes are involved with repairing DNA and preventing tumors, mutations can increase the risk of certain cancers. Approximately 20% to 25% of patients with hereditary breast cancer and 5% to 10% of patients with any type of breast cancer have a BRCA mutation, according to the release.

Olaparib inhibits an enzyme that is involved with repairing damaged DNA. This action prevents DNA inside BRCA-mutated cancer cells from being repaired, which can stop tumor growth.

“This new approval for LYNPARZA makes it the first and only PARP inhibitor approved in metastatic breast cancer, and the only PARP inhibitor approved outside of ovarian cancer," said Dave Fredrickson, executive vice president, head of the oncology business unit, AstraZeneca. "This is significant for breast cancer patients, as the identification of BRCA status, in addition to hormone receptor and HER2 status, becomes a potentially critical step in the management of their disease.”

Olaparib was first approved in 2014 for ovarian cancer and has now received approval to treat patients with germline BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who were previously administered chemotherapy, according to the FDA.

The FDA also expanded the approval of the BRACAnalaysis CDx as a companion diagnostic for these patients.

The safety and efficacy of the treatment were evaluated in a randomized clinical trial that included 302 patients with HER2-negative BRCA-mutated metastatic breast cancer.

The researchers found that the median progression-free survival for patients treated with olaparib was 7 months compared with only 4.2 months for patients treated with chemotherapy, according to the release.

The FDA reported that common side effects of olaparib include anemia, neutropenia, leukopenia, nausea, fatigue, vomiting, nasopharyngitis, respiratory tract infection, influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, and stomatitis.

Serious side effects of the drug include development of myelodysplastic syndrome or acute myeloid leukemia and pneumonitis.

The FDA previously granted olaparib with priority review for this designation.

“This additional approval for LYNPARZA, based on the compelling data from the OlympiAD trial, represents an important advance for women with germline BRCA-mutated HER2-negative metastatic breast cancer, which is a difficult-to-treat cancer. Moreover, this approval adds further impetus to our important collaboration with AstraZeneca in developing cancer therapies," said Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.