AstraZeneca and Merck submitted a new drug application to Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) seeking the approval of Lynparza (olaparib) tablets for the treatment of patients with unresectable or recurrent BRCA-mutated breast cancer. A decision by the agency is expected by the end of 2018.
This is the second new drug application for Lynparza submitted to the Japanese regulatory agency, which is currently reviewing the drug as an ovarian cancer treatment.
AstraZeneca and Merck also filed an application with the U.S. Food and Drug Administration earlier this month, requesting Lyparza approval for a similar breast cancer indication.
The submissions were based on data from the OlympiAD Phase 3 trial (NCT02000622), where Lynparza was shown to significantly delay cancer progression in HER2-negative, BRCA-mutated metastatic breast cancer patients, compared to standard chemotherapy.
The results were recently published in The New England Journal of Medicine in the study, “Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.”
Lynparza, an oral PARP inhibitor, is already approved by the FDA for patients with recurrent ovarian cancer whose tumors carry a mutation in the BRCA gene. But preclinical data suggests it could also lead to positive outcomes in other BRCA-mutated cancers.
The OlympiAD trial, conducted by researchers at Memorial Sloan-Kettering Cancer Center and colleagues at other international institutions, enrolled 302 patients with HER2-negative, BRCA-mutated metastatic breast cancer, who had received one or two prior chemotherapy regimens.
Participants were randomly assigned Lynparza tablets (300 mg twice daily) or a chemotherapy chosen by the physician — either Xeloda (capecitabine), Navelbine (vinorelbine), or Halaven (eribulin).
The study’s primary goal was to assess the time to disease progression or death, or progression-free survival. Secondary measures included overall survival, objective response rate, and time to second progression.
Patients in the Lynparza group lived for a median of 7.0 months without disease progression, compared to 4.2 months among those receiving chemotherapy. This meant that Lynparza reduced the risk of disease progression by 42%. The response rate was also higher in the Lynparza arm — 59.9% vs. 28.8%.
More patients in the chemotherapy arm experienced serious (grade 3 or higher) adverse events (50.5%) compared to those in the Lynparza group (4.9%).
“Among patients with HER2-negative metastatic breast cancer and a germline BRCA mutation, olaparib monotherapy provided a significant benefit over standard therapy,” the study concluded. “Larger studies that investigate the differential treatment effects of olaparib among subgroups, particularly those defined according to hormone-receptor status or previous use of platinum-based therapy, would be helpful.”