Adjuvant bevacizumab could delay ovarian cancer progression
MedWire News: Treatment with bevacizumab as an addition to standard chemotherapy could delay the progression of advanced epithelial ovarian cancer, two studies in The New England Journal of Medicine suggest.
These findings indicate that bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, could be used as a front-line treatment option for patients with advanced ovarian cancer, say the authors of one of the studies, Robert Burger (Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA) and colleagues.
Burger et al conducted a double-blind, placebo-controlled trial in which they randomly allocated 1873 women with newly diagnosed stage III (defined as incompletely resectable) or stage IV epithelial ovarian cancer who underwent debulking surgery, to one of three treatment regimens.
Each regimen comprised 22 3-week cycles using intravenous infusions on day 1, with the first six cycles consisting of standard chemotherapy using carboplatin and paclitaxel.
The control treatment comprised chemotherapy with placebo added in cycles 2 through 22, while bevacizumab-initiation treatment consisted of chemotherapy with bevacizumab (15 mg/kg) added in cycles 2 through 6 and placebo added in cycles 7 through 22. The third regimen, bevacizumab-throughout treatment, comprised chemotherapy with bevacizumab added in cycles 2 through 22.
The primary study endpoint, median progression-free survival, was longer in the bevacizumab-throughout group, at 14.1 months, than the bevacizumab-initiation and control groups, at 11.2 and 10.3 months, respectively.
Patients who received bevacizumab-initiation treatment had a nonsignificant 9% lower risk for disease progression or mortality than control patients, while those who underwent bevacizumab-throughout treatment had a significant 28% lower risk for progression or mortality.
Rates of hypertension requiring medical therapy and gastrointestinal wall disruption requiring medical intervention were significantly higher in the bevacizumab-throughout and bevacizumab-initiation groups, than in the control group.
In the second study, Amit Oza, from the University of Toronto in Ontario, Canada, and colleagues randomly allocated 1528 women with ovarian cancer to receive treatment with carboplatin or paclitaxel every 3 weeks for six cycles, or to this regimen plus bevacizumab (7.5 mg/kg) concurrently every 3 weeks for five or six cycles and continued for 12 additional cycles or until progression of disease.
The results of this phase III trial were similar to that of Burger and team's study. Indeed, the mean progression-free survival at 36 months with standard therapy was significantly lower than with bevacizumab, at 20.3 months versus 21.8 months.
There was also a significant association between bevacizumab and hypertension.
Notably, in patients at high risk for progression (International Federation of Obstetricians and Gynaecologists [FIGO] stage IV disease/FIGO stage III disease and >1.0 cm residual disease after debulking), the benefit was greater with bevacizumab than without it, with a mean progression-free survival at 42 months of 14.5 months with standard therapy alone, and 18.1 months with bevacizumab added.
In a press statement, Oza commented: "This is the first new drug in ovarian cancer in 15 years to improve outcome and I believe it should be considered as a potential new standard of care."
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By Piriya Mahendra