The FDA has approved olaparib (Lynparza, AstraZeneca/Merck) for use in patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been previously treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor positive (HR+) breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Patients are selected for therapy based on an FDA-approved companion diagnostic from Myriad Genetics.
Olaparib is the first PARP inhibitor approved beyond ovarian cancer.
The approval was based on data from the randomized, open-label, phase 3 OlympiAD trial, which investigated olaparib versus physician’s choice of chemotherapy (capecitabine, eribulin, or vinorelbine). In the trial, olaparib significantly prolonged progression-free survival (PFS) compared with chemotherapy, and reduced the risk of disease progression or death by 42% (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.43–0.80; P = 0.0009). Median PFS was 7.0 for olaparib versus 4.2 months for chemotherapy.
Patients with measurable disease taking olaparib (n = 167) experienced an objective response rate of 52% (95% CI, 44–60), double the response rate for those in the chemotherapy arm (n = 66) which was 23% (95% CI, 13–35). Additionally, patients experienced a confirmed complete response rate of 7.8% for olaparib compared to 1.5% for the chemotherapy arm. The data from the OlympiAD trial can be found in the June 2017 issue of the New England Journal of Medicine.
Dr. Susan M. Domchek, Executive Director of the Basser Center for BRCA at the Abramson Cancer Center of the University of Pennsylvania and a national leader on the OlympiAD trials, said: “Patients diagnosed with BRCA-related metastatic breast cancer are often younger than other breast cancer patients, and their disease is often much more aggressive and difficult to treat. While there is currently no cure for metastatic breast cancer, today’s approval offers a new, targeted option that may help to delay disease progression for these patients.”
The most common adverse reactions (20% or more) in the OlympiAD trial of patients who received olaparib were nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%) and headache (20%). The percentage of patients who discontinued treatment in the olaparib arm was 5% compared to the chemotherapy arm, which was 8%.
This is the third indication approved for Lynparza in the U.S., where it has been used to treat nearly 4,000 advanced ovarian cancer patients. AstraZeneca and Merck are working together to deliver Lynparza as quickly as possible to more patients across multiple settings, including breast, ovarian, prostate, and pancreatic cancers.
Source: AstraZeneca/Merck; January 12, 2018.