The Lynparza approval isn’t as broad as the Zejula approval, with Lynparza not approved for use in patients with homologous recombination deficiencies.
The U.S. Food and Drug Administration (FDA) approved AstraZeneca and Merck’s Lynparza (olaparib) in combination with Roche’s Avastin (bevacizumab) for the maintenance treatment of adults with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer has been tested to have either a deleterious or suspected deleterious BRCA mutation and/or genomic instability.
About 50% of women with advanced ovarian cancer have an HRD-positive tumor. For this patient group, first-line treatment is focused on delaying disease progression for as long as possible in hopes of achieving long-term remission.
The approval was built on a biomarker subgroup analysis from the Phase III PAOLA-1 clinical trial, which demonstrated that Lynparza and bevacizumab decreased the risk of disease progression or death by 67%. Adding Lynparza also improved progression-free survival (PFS) to a median of 37.2 months compared to 17.7 months with bevacizumab alone in patients with HRD-positive advanced ovarian cancer.
“Ovarian cancer is a devastating disease,” said Isabelle Ray-Coquard, principal investigator of the PAOLA-1 trial and medical oncologist, Centre Leon Berard and president of the GINECO group. “The magnitude of benefit in HRD-positive patients in the PAOLA-1 trial is impactful. The combination of Lynparza and bevacizumab now provides women with HRD-positive advanced ovarian cancer with a new standard of care and I look forward to seeing this translate into clinical practice.”
As a result of the approval, Merck will pay AstraZeneca $100 million in Collaboration Revenue.
Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor. It is approved for first-line maintenance BRCAm advanced ovarian cancer, first-line maintenance HRD positive advanced ovarian cancer in combination with bevacizumab, maintenance of recurrent ovarian cancer, advanced gBRCAm ovarian cancer, gBRCAm, HER2-negative metastatic breast cancer, and first-line maintenance gBRCAm metastatic pancreatic cancer.
Prior to last week, there were no drugs approved for this indication. Last week, the FDA approved GlaxoSmithKline’s Zejula (niraparib) as a once-daily PARP inhibitor in first-line monotherapy maintenance treatment for women with platinum-responsive advanced ovarian cancer regardless of biomarker status. As with Lynparza, this included advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer patients who are in complete or partial response to first-line platinum-based chemotherapy regardless of biomarker status.
The Lynparza approval isn’t as broad as the Zejula approval, with Lynparza not approved for use in patients with homologous recombination deficiencies (HRD). The Lynparza-Avastin combination therapy only decreased the risk of disease progression or death for this group by 8%.
Andrew Berens, an analyst with Leerink Partners, wrote in a note to clients on Friday, “We have modeled Zejula as having the best commercial opportunity in the HRD-cohort, where the drug will need to compete with Avastin to gain market share.”
Dave Fredrickson, executive vice president of AstraZeneca’s Oncology Business Unit, said, “This approval presents another milestone for Lynparza in patients with ovarian cancer. The median progression-free survival of more than three years offers new hope for more women to delay relapse in this difficult-to-treat disease. These results further establish that HRD-positive is a distinct subset of ovarian cancer, and HRD testing is now a critical component for the diagnosis and tailoring of treatment for women with advanced ovarian cancer.”
