Zejula-Bevacizumab Combo Delays Progression in Relapsed Ovarian Cancer, Trial Finds

Zejula-Bevacizumab Combo Delays Progression in Relapsed Ovarian Cancer, Trial Finds
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A combination of bevacizumab and Zejula (niraparib) is significantly better than Zejula alone at extending the time without disease progression in people with platinum-sensitive relapsed ovarian cancer, findings from a clinical trial show.

The combination also delayed the need for subsequent treatment by prolonging time without disease worsening, and showed a trend toward better survival rates, the researchers noted.

These data were shared at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting — which was held virtually due to the COVID-19 pandemic — in the study, “Final survival analysis of NSGO-AVANOVA2/ENGOT-OV24: Combination of niraparib and bevacizumab versus niraparib alone as treatment of recurrent platinum-sensitive ovarian cancer—A randomized controlled chemotherapy-free study.”

Bevacizumab, marketed as Avastin among other brand names, is an anti-angiogenic therapy that works by preventing tumors from growing new blood vessels, effectively starving these cells. Zejula is a PARP inhibitor marketed by Tesaro (a subsidiary of GlaxoSmithKline); it works by blocking DNA repair, ultimately causing cancer cells to die.

The combination is being investigated in the AVANOVA Phase 1/2 clinical trial (NCT02354131) in women who received at least one prior therapy and responded to platinum-based chemotherapy.

The trial, sponsored by the Nordic Society for Gynaecologic Oncology, enrolled 97 women and randomly assigned them to  either bevacizumab in combination with Zejula or to Zejula alone.

Zejula was given at a dose of 300 mg, taken by mouth once per day. Avastin was given intravenously (into the vein) at a dose of 15 mg/kg once every three weeks. Treatment was administered until signs of disease progression were evident.

AVANOVA’s main goal was to determine whether the addition of bevacizumab extended the time patients lived without their disease getting worse, a measure called progression-free survival (PFS). Exploratory measures included analysis by mutational status, time to subsequent therapy, progression-free survival on that therapy, and overall survival.

Patients given the combination lived a median of 12.5 months without their disease worsening, compared with 5.5 months for those on Zejula only, results showed. This represented a 66% reduction in the risk of disease progression or death.

The combination worked similarly well in patients with and without homologous recombination deficiency, a feature that often predicts better responses to PARP inhibitors like Zejula, because it makes cancer cells worse at repairing their own DNA when it is damaged.

Once the disease progressed, patients were given other treatments. But those on the combination took significantly longer to require their first subsequent therapy compared with those given Zejula only — 14.3 months vs. 7.2 months.

Patients also remained alive and progression-free on that subsequent therapy longer (20.5 months) than those on Zejula alone (15.7 months). Similarly, the time to a second subsequent therapy was better among the group also treated with bevacizumab.

Because of the way the study was designed, researchers could not make statistically meaningful conclusions about overall survival. Rather, they have observed a trend toward better survival outcomes among patients given the combination therapy.

No significant differences were observed between the two groups in quality of life, as assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire and the OV28.

Most adverse events occurred with similar frequency in both treatment groups. The most commonly reported included anemia, fatigue, and gut-related symptoms.

High blood pressure was more common in patients given the combination treatment (22.9% vs. 0%), as was low levels of neutrophils (a type of immune cell), a condition referred to as neutropenia (8.3% vs. 2.0%).

Overall, the findings demonstrate “that the niraparib-bevacizumab combination had clinically and statistically meaningful activity in PSROC [platinum-sensitive relapsed ovarian cancer],” the researchers concluded.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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