The U.S. Food and Drug Administration (FDA) has agreed to review the use of Lynparza (olaparib) tablets as a maintenance treatment for women newly diagnosed with advanced ovarian cancer, Merck announced in a press release.
The application, which is for women with BRCA mutations in complete or partial response after standard first-line platinum-based chemotherapy, received priority review status. A decision is expected in early 2019.
Lynparza, a PARP enzyme inhibitor, acts by preventing cells from repairing their DNA errors. The faster division rate of these cancer cells makes them accumulate errors faster than healthy cells, causing their death. The therapy is particularly effective in cancers with mutations in DNA-repairing genes, such as BRCA1 and BRCA2.
According to AstraZeneca and Merck — known as MSD outside the U.S. and Canada — this is the first time a PARP inhibitor was given regulatory consideration in the U.S. as first-line maintenance treatment for advanced ovarian cancer. If approved, this will be the fourth indication for Lynparza in the U.S.
The therapy is currently approved in over 60 countries for platinum-sensitive relapsed ovarian cancer, regardless of BRCA mutations. It is also indicated for women with BRCA-mutated, advanced ovarian cancer treated with at least three prior chemotherapy treatments, and as a maintenance therapy for women with BRCA-mutated relapsed ovarian cancer whose tumors responded to platinum-based chemotherapy.
The submission was based on findings from a double-blinded, multicenter Phase 3 trial (NCT01844986), named SOLO-1. It compared the efficacy and safety of Lynparza tablets, 300 mg twice daily, to placebo as maintenance therapy in women with advanced ovarian cancer who had a complete or partial response to their first-line chemotherapy.
It included 391 patients, 260 on Lynparza and 131 on placebo, with a mutation in BRCA1, BRCA2, or both genes. The treatment period lasted up to two years or until disease progression.
The study’s primary objective was the time patients lived without cancer progression, a measure called progression-free survival (PFS). Secondary objectives included time to second progression event, overall survival, and quality of life.
After a median follow-up of almost 3.5 years, treatment with Lynparza led to a clinically meaningful improvement in PFS, reducing the risk of disease progression or death by 70%, compared to placebo.
While patients on placebo experienced disease progression or death after a median of 13.8 months, most of those on Lynparza were still alive and disease-free. Lynparza was also associated with a 50% lower risk of progression or death among patients who progressed and received a second treatment course.
SOLO-1 results were recently presented at the European Society of Medical Oncology (ESMO) 2018 Congress, held in Munich, and were published in The New England Journal of Medicine.