Incorporation of bevacizumab in the primary treatment of ovarian cancer.
Author(s): Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS,
Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX; Gynecologic
Oncology Group.
Affiliation(s): Fox Chase Cancer Center, Philadelphia, PA 19111, USA. robert.a.burger@fccc.edu
Publication date & source: 2011, N Engl J Med. , 365(26):2473-83
BACKGROUND: Vascular endothelial growth factor is a key promoter of angiogenesis
and disease progression in epithelial ovarian cancer. Bevacizumab, a humanized
anti-vascular endothelial growth factor monoclonal antibody, has shown
single-agent activity in women with recurrent tumors. Thus, we aimed to evaluate
the addition of bevacizumab to standard front-line therapy.
METHODS: In our double-blind, placebo-controlled, phase 3 trial, we randomly
assigned eligible patients with newly diagnosed stage III (incompletely
resectable) or stage IV epithelial ovarian cancer who had undergone debulking
surgery to receive one of three treatments. All three included chemotherapy
consisting of intravenous paclitaxel at a dose of 175 mg per square meter of
body-surface area, plus carboplatin at an area under the curve of 6, for cycles 1
through 6, plus a study treatment for cycles 2 through 22, each cycle of 3 weeks'
duration. The control treatment was chemotherapy with placebo added in cycles 2
through 22; bevacizumab-initiation treatment was chemotherapy with bevacizumab
(15 mg per kilogram of body weight) added in cycles 2 through 6 and placebo added
in cycles 7 through 22. Bevacizumab-throughout treatment was chemotherapy with
bevacizumab added in cycles 2 through 22. The primary end point was
progression-free survival.
RESULTS: Overall, 1873 women were enrolled. The median progression-free survival
was 10.3 months in the control group, 11.2 in the bevacizumab-initiation group,
and 14.1 in the bevacizumab-throughout group. Relative to control treatment, the
hazard ratio for progression or death was 0.908 (95% confidence interval [CI],
0.795 to 1.040; P=0.16) with bevacizumab initiation and 0.717 (95% CI, 0.625 to
0.824; P<0.001) with bevacizumab throughout. At the time of analysis, 76.3% of
patients were alive, with no significant differences in overall survival among
the three groups. The rate of hypertension requiring medical therapy was higher
in the bevacizumab-initiation group (16.5%) and the bevacizumab-throughout group
(22.9%) than in the control group (7.2%). Gastrointestinal-wall disruption
requiring medical intervention occurred in 1.2%, 2.8%, and 2.6% of patients in
the control group, the bevacizumab-initiation group, and the
bevacizumab-throughout group, respectively.
CONCLUSIONS: The use of bevacizumab during and up to 10 months after carboplatin
and paclitaxel chemotherapy prolongs the median progression-free survival by
about 4 months in patients with advanced epithelial ovarian cancer. (Funded by
the National Cancer Institute and Genentech; ClinicalTrials.gov number,
NCT00262847.).
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