Lynparza Recommended for Approval in Europe for BRCA-mutated Advanced OC

The Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency (EMA), has recommended that Lynparza (olaparib) be approved as a first-line maintenance therapy for women with BRCA-mutated advanced ovarian cancer, AstraZeneca and Merck announced.

Specifically, the recommendation is for women who are responding, partially or completely, to their initial platinum-based chemotherapy.

The U.S. Food and Drug Administration had already approved the therapy for the same indication in December 2018, establishing Lynparza as the first PARP inhibitor to be approved as a first-line maintenance therapy for BRCA-mutated advanced ovarian cancer.

“There remains a significant unmet need in the treatment of advanced ovarian cancer as 70% of women globally relapse within the first three years after their initial treatment,” Dave Fredrickson, executive vice president and head of the oncology business unit at AstraZeneca, said in a press release.

As cancer cells divide at a faster pace, they’re prone to accumulate more errors in their genome than healthy cells. Lynparza inhibits the poly ADP-ribose polymerase (PARP) enzyme and is designed to prevent cancer cells from repairing their DNA errors, which eventually causes them to die. The therapy is particularly effective in cancers with mutations in other DNA-repairing genes, such as BRCA1 and BRCA2.

Both the CHMP’s recommendation and the FDA’s decision were based on clinical data from SOLO-1, an ongoing double-blinded, multicenter Phase 3 trial (NCT01844986) that is examining whether Lynparza is better than a placebo at extending the time patients live without their disease worsening.

SOLO-1 enrolled 391 patients with high-grade serous or endometrioid ovarian cancer, primarily peritoneal cancer, or fallopian-tube cancer and a BRCA mutation, who were randomly assigned Lynparza tablets, or placebo, twice daily for up to two years.

After a median follow-up of 41 months, only 39% of patients given Lynparza had died or seen their disease progress, compared with 73% of those on placebo. This meant that Lynparza cut by 70% the risk of disease progression or death.

The treatment’s safety profile in SOLO-1 was similar to that seen in prior Lynparza clinical trials, with the most common adverse events being nausea, fatigue, vomiting, anemia, and diarrhea. At the time of the analysis, 88% of patients continued with treatment.

“The results of SOLO-1 demonstrate the potential of using Lynparza earlier in the treatment pathway as a maintenance therapy, and reinforce the importance of identifying a patient’s BRCA mutation status as soon as they are diagnosed,” Fredrickson added.

“Women with advanced ovarian cancer need and deserve new treatment options. In the SOLO-1 trial, Lynparza demonstrated a significant progression-free survival benefit as maintenance treatment for patients with advanced BRCA-mutated ovarian cancer following response to first-line platinum-based chemotherapy,” said Roy Baynes, senior vice president and head of global clinical development, chief medical officer at Merck.

“If approved, this expanded indication could change the way women in Europe with BRCA-mutated advanced ovarian cancer are treated,” Baynes added.

Lynparza is currently available in more than 60 countries for the treatment of platinum-sensitive relapsed ovarian cancer, regardless of BRCA mutation status. It also is used for women with BRCA-mutated advanced ovarian cancer who have received at least three chemotherapy treatments, and as a maintenance therapy for women with BRCA-mutated relapsed ovarian cancer whose tumors responded to platinum-based chemotherapy.

AstraZeneca and Merck — known as MSD outside North America — also are studying a combination of Lynparza and Avastin (bevacizumab) as maintenance therapy for patients with newly diagnosed advanced ovarian cancer, regardless of their BRCA status.

Top-line results of this Phase 3 trial — called PAOLA-1  (NCT02477644) — are expected by the end of 2019.