The decision follows a recommendation by the Committee for Medicinal Products for Human Use (an arm of the European Medicines Agency), making Lynparza available for patients with Stage III or IV breast cancer, whose tumors are human epidermal growth factor receptor 2-negative (HER2-) and positive for BRCA gene mutations.
To receive Lynparza under this indication, patients need to have previously received chemotherapy — anthracycline and a taxane — either before or after surgery, unless they’re unsuitable for such treatments. Also, patients with hormone receptor (HR)-positive cancer should have been treated with or been considered unsuitable for hormone therapy.
Lynparza, developed jointly by AstraZeneca and Merck (known as MSD outside the U.S. and Canada), is a PARP enzyme inhibitor that blocks the DNA repair process in cells. Due to their faster division, cancer cells accumulate errors faster than healthy cells, which, if not repaired, causes their death.
The BRCA1 and BRCA2 genes produce proteins involved in DNA repair. When either of these genes is altered, these proteins may not be made or function correctly, which precludes DNA repair and increases the risk for additional genetic changes that can lead to cancer.
“With this approval, Lynparza provides patients throughout the EU with a targeted and oral chemotherapy-free treatment option for a difficult-to-treat cancer,” Dave Fredrickson, AstraZeneca’s executive vice president of oncology, said in a press release.
He added that this decision “reinforces the importance of testing for biomarkers including BRCA, hormone receptor and HER2 expression, helping physicians to make the most informed treatment decisions for patients.”
Roy Baynes, MD, PhD, Merck Research Laboratories’ senior vice president, head of global clinical development, and chief medical officer, commented: “We look forward to making this new option available across the EU, where we hope it will improve outcomes for many patients.”
The approval was based on results from an ongoing Phase 3 trial named OlympiAD (NCT02000622). This global, open-label study included 302 patients with HER2-negative, locally advanced or metastatic breast cancer, who carried mutations in BRCA1 and/or BRCA2.
All participants had received chemotherapy prior to the study. Also, those with HR-positive tumors had received at least one hormone therapy and had disease progression while on treatment, unless their disease made endocrine therapy inappropriate.
The main goal was to assess whether treatment with 300 mg Lynparza given twice daily could delay disease progression or death, compared with the physician’s choice of chemotherapy — Xeloda (capecitabine), Navelbine (vinorelbine), or Halaven (eribulin).
Secondary goals included time to disease progression or death after a subsequent treatment, overall survival, and objective response rate — which refers to complete response, or disappearance of all cancer signs, and partial response.
Treatment with Lynparza was associated with a significantly longer period without cancer progression — seven months vs. 4.2 months with chemotherapy — which is a 42% reduction in the risk of disease progression or death.
Also, more patients responded to Lynparza (52%) than to chemotherapy (23%). Complete responses were also more common with Lynparza — 9% vs. 1.5% for chemotherapy. However, no benefits were found in overall survival.
The most frequent adverse reactions in patients on Lynparza were nausea (58%), anemia (40%), fatigue (37%), vomiting (30%), reduced neutrophils levels (27%), and respiratory tract infection (27%). Fewer patients discontinued treatment with Lynparza (5%) than with chemotherapy (8%).
Besides their breast cancer program, AstraZeneca and Merck are also developing Lynparza for other indications, including a Phase 3 trial in metastatic pancreatic cancer patients (NCT02184195).
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