FDA Approves Lynparza® Plus Avastin® Combo for Gynecologic Cancers

The U.S. Food and Drug Administration (FDA) approved Lynparza® (olaparib) in combination with Avastin® (bevacizumab) for first-line 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 is associated with homologous recombination deficiency (HRD)-positive status defined by either a deleterious or suspected deleterious BRCA mutation and/or genomic instability. The FDA also approved the Myriad myChoice® CDx as a companion diagnostic for olaparib.

The decision was based on results of the randomized, double-blind, placebo-controlled, multicenter PAOLA-1 trial that included 806 women with advanced high-grade epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer following first-line platinum-based chemotherapy and bevacizumab.

Patients were stratified based on first-line treatment outcome and tumor BRCA mutation status. Patients were randomized 2:1 to receive olaparib 300 mg orally twice daily in combination with bevacizumab 15 mg/kg every three weeks (n=537) or placebo plus bevacizumab (n=269). Patients continued bevacizumab in the maintenance setting and started olaparib after a minimum of three weeks and up to a maximum of nine weeks following their last chemotherapy dose. Olaparib was continued for up to two years or until disease progression or unacceptable toxicity.

Survival improved in olaparib combination cohort

Among patients with BRCA-mutated tumors, median progression-free survival (PFS) was 37.2 months in the olaparib combination group versus 21.7 months in the placebo group (hazard ratio [HR], 0.31; 95% CI, 0.2-0.47). Among women without BRCA mutations, median PFS was 18.9 months in the olaparib combination group versus 16 months in the placebo group (HR, 0.71; 95% CI, 0.58-0.88).

In a subgroup of 387 patients with HRD-positive tumors, estimated median PFS was 37.2 months in the olaparib combination arm versus 17.7 months in the placebo cohort (HR, 0.33; 95% CI, 0.25-0.45). Overall survival data were not mature.

The most common adverse events (AEs) associated with the olaparib and bevacizumab combination were nausea, fatigue (including asthenia), anemia, lymphopenia, vomiting, diarrhea, neutropenia, leukopenia, urinary tract infection, and headache. AEs resulted in dose interruptions in 54% of patients in the olaparib arm, and AEs led to dose reductions in 41% of these patients.