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Olaparib/Bevacizumab Improves Outcomes in BRCA-Negative Ovarian Cancer

Ovarian cancer cells.

A phase 3 trial reports that olaparib as maintenance therapy in combination with bevacizumab increases progression-free survival (PFS) in patients with newly diagnosed, advanced high-grade ovarian cancer both with and without BRCA mutations.

While previous studies have found that maintenance olaparib is associated with improved outcomes in patients with ovarian cancer with BRCA mutations, its efficacy in patients without BRCA mutations had not been confirmed. In the phase 3 PAOLA-1 trial, a team of researchers led by Isabelle Ray-Coquard, MD, PhD, a medical oncologist at the Institute for Clinical Science at the Centre Léon-Bérard in Lyon, France, investigated the benefit of olaparib in combination with bevacizumab in patients with newly diagnosed, advanced high-grade ovarian cancer regardless of BRCA mutation status.

The trial enrolled 806 patients who were randomized in a 2:1 ratio to receive either olaparib/bevacizumab or placebo/bevacizumab. Patients in the experimental group received 300 mg of olaparib twice daily for up to 24 months, and all patients received 15 mg/kg of bevacizumab every 3 weeks for a maximum of 15 months. The study's primary end point was the time from treatment initiation until disease progression or death.

At a median follow-up of 22.9 months, olaparib/bevacizumab significantly improved median PFS compared with placebo/bevacizumab (22.1 months vs 16.6 months). Olaparib/bevacizumab also produced greater PFS in patients whose tumors were homologous-recombination deficiency (HRD)-positive and had BRCA mutations compared with the control group (37.2 months vs 17.7 months), as well as in patients with HRD-positive tumors without BRCA mutations (28.1 months vs 16.6 months).

"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," conclude Dr. Ray-Coquard and colleagues in their study, now published in The New England Journal of Medicine. "[The benefit] was substantial in patients with HRD-positive tumors, including those without a BRCA mutation."

For More Information

Ray-Coquard I, Pautier P, Pignata S, et al (2019). Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med, 381(25):2416-2428. DOI:10.1056/NEJMoa1911361

​Image credit: Nephron. Licensed under CC BY-SA 3.0

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