China OKs Lynparza as Maintenance Therapy for Advanced Ovarian Cancers with BRCA Mutations

Oral Lynparza (olaparib) has been approved in China as a first-line maintenance treatment for women with BRCA-mutated advanced ovarian cancer who responded to initial platinum-based chemotherapy, AstraZeneca and Merck (known as MSD outside the U.S. and Canada) announced.

Lynparza is now the first PARP enzyme inhibitor approved in that country as an initial maintenance treatment for BRCA-mutated advanced ovarian cancer. Similar approvals have been granted in the U.S., Europe, Canada, Brazil and Japan.

“This approval marks a new era for women with BRCA-mutated advanced ovarian cancer in China, where the prevalence of BRCA mutations in advanced disease is higher than the international average,” Dave Fredrickson, executive vice president, oncology business unit, AstraZeneca, said in a press release.

This oral anti-cancer treatment works by blocking the PARP enzyme, which is involved in DNA repair and cancer cell survival and proliferation. It has been found to be particularly effective in patients carrying genetic mutations in the BRCA genes, which also play a role in DNA repair.

The approval by China’s National Medical Products Administration was based on clinical data from the ongoing SOLO-1 Phase 3 trial (NCT01844986), in which Lynparza as a maintenance monotherapy reduced the risk of disease progression or death by 70% compared to a placebo.

SOLO-1 enrolled 391 patients with high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer, who responded, partly or completely, to their first-line platinum-based chemotherapy.

Participants, with either inherited or acquired BRCA mutations, were randomly assigned to Lynparza (260 patients) or a placebo (131 patients), given twice daily for two years or until disease progression.

The study’s primary goal was to determine whether Lynparza was better than a placebo at extending the time patients lived without their disease worsening. Overall survival, changes in quality of life, and safety were examined as secondary measures.

At 36 months, 61% of Lynparza-treated patients were alive and without signs of disease progression, compared to 27% of those on placebo. The median progression-free survival was 13.8 months for those in the placebo group, while most  on Lynparza were still alive and progression-free at the time of the analysis — a median follow-up of 41 months (about 3.4 years).

The safety profile of Lynparza was similar to that seen in prior trials, with the most common adverse events being nausea, fatigue, vomiting, anemia, and diarrhea. At the time of the analysis, 88% of women were still using Lynparza.

“Currently, 70% of women relapse within three years of initial treatment, representing the highest reoccurrence rate among gynecological cancers worldwide. The progression-free survival benefit of Lynparza observed in SOLO-1 is a significant step towards helping these women achieve long-term remission,” Fredrickson said.

“Today’s approval of Lynparza reinforces the importance of patients knowing their BRCA mutation status at diagnosis. We are proud to provide a new option for the treatment of this devastating disease in China,” added Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck.

Another Phase 3 trial, called PAOLA-1 (NCT02477644), is exploring a combination of Lynparza plus Avastin (bevacizumab) in a similar population of ovarian cancer patients, but regardless of their BRCA status. The trial has already met its primary goal, showing that the combination is better than Avastin alone at delaying disease progression or death.

PAOLA-1, conducted across Europe and in Japan, is the second Phase 3 trial — after SOLO-1 — whose findings support Lynparza as a first-line maintenance treatment for patients with advanced ovarian cancer.