The European Medicines Agency (EMA) has approved Lynparza (olaparib) tablets as a maintenance therapy for ovarian cancer patient who have relapsed, but have had a complete or partial response to platinum-based chemotherapy, and regardless of BRCA mutations.
The new formulation of Lynparza as tablets — marketed by AstraZeneca and Merck (MSD outside North America) — was approved to treat high-grade epithelial ovarian, fallopian tube (tube that connects the ovaries to the uterus), or primary cancer of the peritoneum (the membrane lining the abdomen).
This formulation is also approved by the U.S. Food and Drug Administration (FDA) to treat advanced ovarian cancer and certain types of metastatic breast cancer.
European approval follows a positive recommendation issued by the Committee for Medicinal Products for Human Use (CHMP) of the EMA.
While the medicine is particularly effective in cells with deficiencies in DNA damage repair, the recommendation was for patients with or without BRCA mutations, provided they have platinum-sensitive tumors.
The EU first authorized Lynparza as a capsule for women with platinum-sensitive relapsed ovarian cancer and BRCA mutations in 2014. But more recent clinical data supported its effective in also treating women without BRCA mutations, whose tumors are sensitive to platinum-based chemotherapy.
In addition, the new tablet formulation lowers daily dosing from eight capsules to two tablets twice a day.
“With this new approval for Lynparza, we will now be able to offer more women with platinum-sensitive ovarian cancer, regardless of their BRCA status, a chance to achieve long-term disease control with an oral medicine that has a well-characterised safety and tolerability profile,” Dave Fredrickson, AstraZeneca’s executive vice president and head of the oncology business unit, said in a press release.
As with the FDA, EU approval of Lynparza tablets was supported by data from two trials — the SOLO-2 Phase 3 trial (NCT01874353) and the Study 19 Phase 2 trial (NCT00753545). They showed that Lynparza reduces the risk of disease progression or death for platinum-sensitive relapsed ovarian cancer. Data covered efficacy and safety follow-up on Lynparza-treated patients for more than five years.
Results of both trials showed that treatment with Lynparza (300 or 400 milligrams twice a day) led to a 65% to 70% reduction in the risk of disease progression or death.
In the SOLO-2 study, time to disease progression was 19.1 months in treated women compared to 5.5 months in those given a placebo.
Study 19 showed that Lynparza treatment was effective for ovarian cancer patients with or without BRCA mutations. In this trial, women receiving Lynparza had a median time to disease progression of 13.3 months, compared with 6.7 months in the placebo group. Additionally, 13% of the treated patients remained progression-free and on therapy for at least five years.
Across the trials, only 6% to 11% of patients discontinued treatment due to side effects attributed to Lynparza use, the most common being nausea and vomiting, diarrhea, indigestion, fatigue, headache, dizziness, and anemia.
Lynparza is an inhibitor of the poly ADP-ribose polymerase (PARP), an enzyme involved in the repair of DNA damage in cells. Tumor cells respond poorly in a number of DNA repair pathways, including BRCA. In these situations, cancer cells rely on PARP to survive and proliferate.
By blocking the action of PARP, and given the DNA repair defects often present in tumors, Lynparza leads to increased DNA damage and cancer cell death.