Olaparib Plus Bevacizumab Effective Maintenance Therapy in Ovarian Cancer

A new randomized trial evaluated the efficacy of olaparib plus bevacizumab on progression-free survival in women with advanced ovarian cancer, regardless of BRCA mutation.

“Newly diagnosed advanced ovarian cancer is treated with curative intent. However, owing to late diagnosis with advanced-stage disease, the vast majority of patients have a relapse (after a median of 10 to 18 months), despite being treated with cytoreductive surgery and platinum-based chemotherapy,” the study authors wrote.

“Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation,” they added. “The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown.”

The double-blind, phase 3 trial included patients newly diagnosed with advanced, high-grade ovarian cancer responding to first-line platinum-taxane chemotherapy plus bevacizumab; regardless of surgical outcome or whether they had a BRCA mutation. Patients were randomized 2:1 to receive olaparib 300 mg twice daily or placebo for up to two years. Both groups received bevacizumab 15 mg per kilogram of body weight every three weeks for up to 15 months. The main outcome was time to progression or death.

Final analysis included 806 patients: 537 in the olaparib group and 269 in the placebo group. Median follow-up time was 22.9 months, at which time median progression-free survival was 22.1 months in the olaparib plus bevacizumab group compared to 16.6 months in the placebo plus bevacizumab group (hazard ratio [HR] for disease progression or death=0.59; 95% confidence interval [CI], 0.49-0.72; P<0.001). in patients with homologous-recombination deficiency (HRD)-positive tumors, including those with BRCA mutations, the HR for disease progression or death in the olaparib group compared to the placebo group was 0.33 (95% CI, 0.25-0.45); median progression-free survival was 37.2 months versus 17.7 months, respectively. In HRD-positive tumor patients who did not have a BRCA mutation, the HR was 0.43 (95% CI, 0.28-0.66 median progression-free survival, 28.1 months vs. 16.6 months, respectively). No new safety signals were observed for olaparib or bevacizumab.

The olaparib and placebo groups had similar mean baseline global health status-quality of life scores (68.6 points vs. 67.1 points). In the olaparib group, the mean change from baseline was –1.33 points, compared to –2.89 points in the placebo group, for an estimated between-group difference of 1.56 points—not considered clinically significant, the authors noted.

The study was published in The New England Journal of Medicine.

The researchers concluded, “Administering maintenance olaparib in addition to bevacizumab to patients with newly diagnosed advanced ovarian cancer who were receiving standard treatment including bevacizumab resulted in a significant progression-free survival benefit, with a substantial benefit in patients with HRD-positive tumors. Previously defined toxic effects of olaparib and bevacizumab were noted, and rare serious hematologic and mild-to-moderate pulmonary toxic effects also occurred.”