June 5, 2011 (Chicago, Illinois) — Adding bevacizumab (Avastin) to standard chemotherapy might offer a survival benefit for women with newly diagnosed ovarian cancer. Although the data are still too early to provide a definitive answer, they do appear to be very promising, researchers reported here at the American Society of Clinical Oncology 2011 Annual Meeting.
This was 1 of 2 studies on bevacizumab in ovarian cancer highlighted at a press briefing. The other was the phase 3 OCEANS trial conducted in women with recurrent disease. This builds on previous studies that are being amassed to support the filing for the approval of ovarian cancer as a new indication for the drug.
Gunnar Kristensen, MD, PhD, senior consultant in the Department for Gynecologic Oncology, Norwegian Radium Hospital in Oslo, reported the results from women with newly diagnosed ovarian cancer.
"We have not made progress in at least 15 years with this disease," he said. "The first new front-line treatment is bevacizumab. We are now presenting an interim analysis of overall survival and an updated analysis of progression-free survival."
At a median follow-up of 28 months, there were fewer deaths among patients who received bevacizumab than among those who received standard chemotherapy (178 vs 200). Although this represents a 15% overall reduction in mortality risk, the difference did not reach statistical significance (hazard ratio [HR], 0.85; P = .11).
In the updated analysis, patients in the bevacizumab group had longer progression-free survival than those in the control group (19.8 vs 17.4 months; HR, 0.87; P = .039).
"There is a substantial prolongation of time to progression," said Dr. Kristensen, adding that the gain was 2.4 months.
Beneficial to High-Risk Group
The authors also conducted an exploratory subgroup analysis of patients with a poor prognosis, defined as International Federation of Gynecology and Obstetrics (FIGO) stage III debulked to more than 1.0 cm, or FIGO stage IV with debulking. Within this subgroup, there were 79 deaths in the bevacizumab group and 109 deaths in the standard group, for a 36% reduction in risk for death (HR, 0.64; P = 0.0002; P = .015 for test for interaction [treatment/risk group]). This result was statistically significant.
"We have previously shown that [the high-risk] group has a greater benefit from bevacizumab than the other patients," said Dr. Kristensen. "For this group, there is a very clear gain for overall survival."
Update of Earlier Results
The ICON7 trial investigated the safety and efficacy of adding bevacizumab to standard chemotherapy in women with newly diagnosed ovarian cancer, and the first results were presented at last year at the annual meeting of the European Society of Medical Oncology.
At that time, an analysis of mature progression-free survival data suggested a benefit from bevacizumab. As reported by Medscape Medical News, at 12 months, women who received bevacizumab plus carboplatin and paclitaxel had a 15% lower risk for disease progression than those who received chemotherapy alone (P = .0041).
There was also a trend toward overall survival (HR, 0.81; P = .098).
The final analyses for overall survival will be performed when 715 deaths have occurred, note the authors. The current analysis was conducted because an interim analysis with at least 365 deaths was requested by regulatory authorities — the US Food and Drug Administration and the European Medicines Agency — for licensing consideration.
A total of 1528 women from 263 centers in 7 Gynecologic Cancer InterGroup (GCIG) groups with high-risk early (FIGO stage I or IIa, capped at 10% or below) or advanced (stage IIb to IV) epithelial ovarian, primary peritoneal, or fallopian tube cancer were included in the study. Within this group, 9% had high-risk early-stage disease and 30% had a poor prognosis.
Patients were randomized in a 1:1 ratio to 1 of 2 treatment groups: 6 cycles of chemotherapy alone 3 times weekly (carboplatin area under the curve [AUC] 5 or 6 and paclitaxel 175 mg/m2); or the same chemotherapy given concurrently with bevacizumab (7.5 mg/kg) for 5 or 6 cycles, followed by continued single-agent bevacizumab 3 times weekly for 12 additional cycles or until disease progression.
"We conclude that the addition of concurrent and continued bevacizumab for 12 months does improve progression-free survival," said Dr. Kristensen, adding that on the basis of an interim analysis of 375 deaths — 53% of the number needed for the final analysis — there is an overall trend for improvement in overall survival.
"In this study, we see the ability of antiangiogenic therapy to delay the progression of ovarian cancer, this time in the first-line setting," said Andrew Seidman, MD, professor of medicine at Weill Medical College of Cornell University in New York City.
He added that previous studies have demonstrated the efficacy of bevacizumab in ovarian cancer. "These lend support to a potential role for bevacizumab as the first biologic agent to be used in this disease," said Dr. Seidman, who moderated a press briefing at which the highlights of this study were presented.
There are many strengths in a study like this, in that it addresses questions about the role of anti-VEGF therapies in this setting, said Anil Sood, MD, who served as a discussant for this paper. "The randomized design is obviously a major strength.
However, there are some issues to consider, explained Dr. Sood, who is professor and director of the Blanton-Davis Ovarian Cancer Research Program in the Departments of Gynecologic Oncology and Cancer Biology at the University of Texas M.D. Anderson Cancer Center, in Houston. "One is the role of bevacizumab in the combination setting, compared with the maintenance setting."
"How useful is bevacizumab in the combination setting up front? Is the real role for bevacizumab in the maintenance setting following initial chemotherapy," he asked.
The issue of bevacizumab dosing should also be considered, Dr. Sood noted. "One of the questions is whether higher doses are needed," he said. "There are data emerging from other studies showing that lower doses are as efficacious, if not more so."
Dr. Kristensen reports serving as a consultant or advisor for Roche. Dr. Seidman reports serving as a consultant or advisor for Enzon and Wyeth; receiving honoraria from Abraxis BioScience, Genentech, and Genomic Health; and receiving research funding from Abraxis BioScience. Dr. Sood has disclosed no relevant financial relationships.
American Society of Clinical Oncology (ASCO®) 2011 Annual Meeting: Abstract LBA5006. Presented June 4, 2011.
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Cite this: First-Line Bevacizumab Improves Survival in Ovarian Cancer - Medscape - Jun 05, 2011.