EMA to Decide if Lynparza Can Treat BRCA-mutated Metastatic Breast Cancer Patients

EMA to Decide if Lynparza Can Treat BRCA-mutated Metastatic Breast Cancer Patients

The European Medicines Agency has agreed to review an application by AstraZeneca and MSD requesting the approval of Lynparza (olaparib) for the treatment of patients with a difficult-to-treat type of metastatic breast cancer who previously received chemotherapy.

The Marketing Authorization Application for Lynparza is supported by the results of the Phase 3 OlympiAD clinical trial (NCT02000622), which compared the safety and effectiveness of Lynparza tablets (300 mg taken twice daily) to physician’s choice chemotherapy — Xeloda (capecitabine), Navelbine (vinorelbine), or Halaven (eribulin). All patients had previously been treated with chemotherapy.

The global, multi-center study included 302 patients (205 received Lynparza) who were either triple negative — meaning their cancer did not produce human epidermal growth factor receptor 2 (HER2), estrogen receptors (ER), and progesterone receptors (PR) — or were positive for hormone receptor (HR), which means PR or ER activity.

Tests for the presence of these receptors indicates which hormones or other proteins may be promoting the cancer.

Treatment with Lynparza decreased the risk of disease progression or death by 42% compared to chemotherapy. It also induced a response in 52% of patients, compared to 23% in the chemotherapy group.

Among those who responded, Lynparza led to the complete cancer elimination in 7.8% of patients, while 1.5% of patients treated with chemotherapy had a similar disease remission.

The research, “Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation,” was published in the New England Journal of Medicine. 

Breast cancer is the most frequent cancer in women. About 30% of patients diagnosed with early breast cancer progress to advanced disease. Despite an increase in treatments able to slow its progression, metastatic breast cancer currently has no cure.

Mutations in the BRCA1 and BRCA2 genes lead to the lack or abnormal function of proteins responsible for repairing DNA damage, which may make cells become unstable and develop additional genetic alterations that can result in cancer.

Lynparza is a PARP inhibitor that blocks the DNA repair process. The PARP enzyme is particularly relevant for DNA repair in people with BRCA mutations, and blocking it prevents the survival of tumors.

According to AstraZeneca and MSD (known as Merck in the U.S. and Canada), this is the first European regulatory submission for a PARP inhibitor in breast cancer. Identifying a patient’s BRCA status could become a key step for disease management, along with the evaluation of hormone receptor and HER2 status, the companies stated in a press release.

In January, the U.S. Food and Drug Administration approved Lynparza for the treatment of BRCA-mutated HER2-negative metastatic breast cancer.

The FDA had initially approved the medication for the treatment of BRCA-mutated advanced ovarian cancer.

According to AstraZeneca and MSD, which co-developed and commercialized Lynparza, the therapy has the broadest clinical development program of any PARP inhibitor. 

Lynparza is currently available in approximately 60 countries and has been used to treat more than 20,000 patients, the companies stated.