As reported in The New England Journal of Medicine by Isabelle Ray-Coquard, MD, PhD, and colleagues, the phase III PAOLA-1 trial has shown a progression-free survival benefit with the addition of olaparib to bevacizumab maintenance in patients with advanced ovarian cancer responding to first-line platinum-taxane chemotherapy plus bevacizumab. The benefit was greatest in patients with homologous recombination deficiency (HRD)-positive tumors, including those without a BRCA mutation.
Isabelle Ray-Coquard, MD, PhD
Study Details
In the double-blind trial, 806 women from sites in 11 countries with newly diagnosed advanced high-grade ovarian cancer who responded to first-line platinum-taxane chemotherapy plus bevacizumab were randomly assigned 2:1 between July 2015 and September 2017 to receive 300 mg of olaparib twice daily (n = 537) or placebo (n = 269) for up to 24 months. All patients received bevacizumab maintenance at 15 mg/kg every 3 weeks for up to a total of 15 months. Patients were enrolled irrespective of BRCA status. The primary endpoint was investigator-assessed progression-free survival.
Progression-Free Survival
Median follow-up was 22.9 months. Median progression-free survival was 22.1 months in the olaparib group vs 16.6 months in the placebo group (hazard ratio [HR] = 0.59, P < .001).
In subgroup analysis by BRCA status, median progression-free survival was 37.2 months vs 21.7 months among 157 patients treated with olaparib vs 80 patients treated with placebo with a BRCA mutation (HR = 0.31, 95% confidence interval [CI] = 0.20–0.47) and 18.9 vs 16.0 months among 380 vs 189 patients without a BRCA mutation (HR = 0.71, 95% CI = 0.58–0.88).
KEY POINTS
- The addition of olaparib to bevacizumab maintenance was associated with improved progression-free survival.
- Benefit was greatest in HRD-positive patients, including those without a BRCA mutation.
In analysis by HRD status, median progression-free survival was 37.2 vs 17.7 months (HR = 0.33, 95% CI = 0.25–0.45) among 255 vs 132 patients with HRD-positive tumors including those with a BRCA mutation and 28.1 vs 16.6 months among 97 vs 55 patients with HRD-positive tumors without a BRCA mutation (HR = 0.43, 95% CI = 0.28–0.66). Among 192 vs 85 patients with HRD-negative tumors, median progression-free survival was 16.6 vs 16.2 months (HR = 1.00, 95% CI = 0.75–1.35).
Adverse Events
According to the investigators, adverse events were consistent with the known safety profiles of olaparib and bevacizumab. During maintenance therapy, the most common adverse events of any grade occurring more frequently in the olaparib group were fatigue, nausea, and anemia. Serious adverse events occurred in 31% of both groups.
The investigators concluded, “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.”
Dr. Ray-Coquard, of Centre Léon Bérard, Lyon, France, is corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by ARCAGY Research, AstraZeneca, Merck Sharp & Dohme (a subsidiary of Merck), and F. Hoffmann–La Roche. For full disclosures of the study authors, visit nejm.org.
