In women with newly diagnosed advanced ovarian cancer, frontline maintenance therapy with olaparib (Lynparza) plus bevacizumab (Avastin) reduced the risk for a progression event by 41% compared with bevacizumab and placebo. The reduction in risk with olaparib plus bevacizumab was even greater in the BRCA-mutated subset of women (68.6% reduction in risk), and in those with homologous recombination deficiency (HRD-positive tumors; 67.1% reduction in risk), according to data from the phase 3 PAOLA-1 clinical trial.
With a median follow-up of 22.9 months, median progression-free survival (PFS) increased from 16.6 months in the bevacizumab/placebo arm up to 22.1 months in the combination arm (hazard ratio [HR], 0.59; P <.001) in the overall intent-to-treat population, reported lead investigator Isabelle Ray-Coquard, MD, PhD, Medical Oncologist, Institute for Clinical Science, Centre Léon Bérard, Lyon, France, at the 2020 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer. The data have also been published in the New England Journal of Medicine (Ray-Coquard I, et al. NEJM. 2019;381:2416-2428).
“We have to note that patients started first-line treatment a median of 7 months before randomization, so patients in this trial receiving chemotherapy and bevacizumab plus olaparib experienced a total median time without progression of almost 30 months,” said Dr Ray-Coquard.
PAOLA-1 evaluated maintenance therapy with olaparib in patients with advanced ovarian cancer—regardless of BRCA mutation status—who were responding to first-line standard-of-care treatment with chemotherapy plus bevacizumab. It enrolled 806 women with newly diagnosed stage III or IV high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer. Patients were randomized 2:1 to receive olaparib 300 mg twice daily for up to 2 years plus bevacizumab 15 mg/kg every 3 weeks for 15 months, or placebo.
Some 30% of patients had BRCA-mutated tumors. In an analysis of PFS by BRCA status, median PFS in the patients who had a BRCA mutation was 37.2 months in those assigned to olaparib versus 21.7 months in those assigned to placebo (HR, 0.31; 95% confidence interval [CI], 0.20-0.47) and 18.9 versus 16.0 months (HR, 0.71; 95% CI, 0.58-0.88), respectively, among those without a BRCA mutation.
Tumor HRD status was positive in 47% of the olaparib group versus 49% in the placebo group, and was unknown in 17% and 19%, respectively. When the outcome was evaluated according to HRD status, including those who had a BRCA mutation, median PFS was 37.2 months in the olaparib arm versus 17.7 months in the placebo arm (HR, 0.33; 95% CI, 0.25-0.45).
Patients with HRD-positive tumors that did not have BRCA mutations also experienced a substantial PFS benefit with the addition of olaparib to bevacizumab, with a median PFS improvement of almost 1 year: 28.1 months versus 16.6 months (HR, 0.43; 95% CI, 0.28-0.66).
There was no significant difference between the 2 treatment arms in median PFS for patients who were HRD-negative or who had an unknown HRD status.