Olaparib Receives FDA Approval for the Treatment of BRCA Mutation-Positive Metastatic Breast Cancer

On January 12, 2018, the United States Food and Drug Administration FDA, approved olaparib tablets (brand name Lynparza), a poly (ADP-ribose) polymerase (PARP) inhibitor, for the treatment of HER2-negative stage 4 breast cancer with a germline BRCA gene mutation in patients who had previously received chemotherapy for neoadjuvant, adjuvant or metastatic disease. This treatment is the germline

First FDA-Approved Treatment for Patients with a BRCA Mutation (gBRCAm) and HER2-Negative Metastatic Breast Cancer.

According to the approval, to use this drug, patients with hormone receptor-positive breast cancer must have previously received hormonal therapy or be considered unsuitable for hormonal therapy.

The approval is based on a randomized, open-label, multicenter clinical trial called OlympiAD, involving patients with gBRCAm and HER2-negative metastatic breast cancer, 302 patients in total, in which olaparib was taken orally as tablets twice daily or chemotherapy chosen by the physician (capecitabine, vinorelbine or eribulin) was used.

Patients included in the study were randomized according to their germline BRCA gene mutation and previous chemotherapy for neoadjuvant, adjuvant or metastatic disease. Randomization (random assignment to groups to avoid bias) was stratified by previous use of chemotherapy for metastatic disease, hormone receptor status (hormone receptor-positive vs. triple-negative) and previous use of platinum-based chemotherapy. The primary efficacy outcome was evaluated by an independent committee through measurement of progression-free survival (PFS); the median periods for which the disease was kept under control (progression-free survival) were found to be 7.0 and 4.2 months in the olaparib and chemotherapy arms, respectively.

In clinical trials reported in at least %20 of patients taking olaparib were the following most common side effects anemia, nausea, fatigue, vomiting, a decrease in white blood cells (leukopenia), upper respiratory tract infection, diarrhea, joint and muscle pain, tinnitus, headache, indigestion, decreased appetite, constipation and infection inside the mouth.

The FDA also approved the BRACAnalysis CDx® test (Myriad Genetic Laboratories, Inc.) for detecting a BRCA gene mutation that may qualify a patient for olaparib.

The recommended olaparib tablet dose is 300 mg (two 150 mg tablets) taken orally twice daily (with or without food).