[HTML][HTML] Olaparib plus bevacizumab as first-line maintenance in ovarian cancer
New England Journal of Medicine, 2019•Mass Medical Soc
Background Olaparib has shown significant clinical benefit as maintenance therapy in
women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of
combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation
status is unknown. Methods We conducted a randomized, double-blind, international phase
3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and
were having a response after first-line platinum–taxane chemotherapy plus bevacizumab …
women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of
combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation
status is unknown. Methods We conducted a randomized, double-blind, international phase
3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and
were having a response after first-line platinum–taxane chemotherapy plus bevacizumab …
Background
Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown.
Methods
We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum–taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or BRCA mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death.
Results
Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95% confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had BRCA mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab.
Conclusions
In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation. (Funded by ARCAGY Research and others; PAOLA-1 ClinicalTrials.gov number, NCT02477644.)
The New England Journal Of Medicine