ICON7 Trial Shows Bevacizumab Increases Survival in Women with Newly Diagnosed Ovarian Cancer

CHICAGO--The addition of bevacizumab to carboplatin and paclitaxel chemotherapy for the first-line treatment of women with ovarian cancer may offer benefit compared with standard chemotherapy alone, particularly for patients with more aggressive disease, investigators noted in a presentation during the American Society of Clinical Oncology's 2011 Annual Meeting.

Approximately 22,000 U.S. women are diagnosed annually with ovarian cancer, which is the fourth most common cause of cancer death in women. Bevacizumab represents the first new active agent for the front-line treatment of ovarian cancer in more than 15 years.

Gunnar Kristensen, MD, PhD, of the Norwegian Radium Hospital, Oslo, Norway, and colleagues presented interim overall survival (OS) results of ICON7. This Phase 3 multicenter trial randomized 1,528 women with newly diagnosed high-risk or advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer to receive 6 cycles of chemotherapy alone (carboplatin AUC 5 or 6 + paclitaxel 175mg/m2) followed by observation or the same chemotherapy concurrently with bevacizumab 7.5mg/kg every 3 weeks for six cycles followed by single-agent bevacizumab for a total duration of 18 cycles (12 months).

Baseline characteristics were balanced between treatment groups. Median age was 57 years (range, 18–81 years) in the chemotherapy group and 57 years (range, 24–82) in the bevacizumab group. Ovarian cancer origin was epithelial in 87% of the group that received chemotherapy and 88% of those receiving bevacizumab.

Initial results at a median follow-up of 19 months, presented at the European Society of Medical Oncology's 2010 Annual Meeting, found an improved progression-free survival (PFS) when bevacizumab was added to standard chemotherapy. Analyses of mature PFS data, at a median follow-up of 36 months, continue to suggest a benefit from bevacizumab: PFS was 19.8 months in the bevacizumab group vs. 17.4 months in the chemotherapy group (HR 0.87 [0.77–0.99]; P=0.039).

Results of an updated interim OS analysis, requested by regulatory authorities considering the licensing application for use of bevacizumab in ovarian cancer, found that at a median follow-up of 28 months, there were fewer deaths in the bevacizumab group than in the group receiving standard chemotherapy, 178 vs. 200, respectively (HR 0.85 [0.69–1.04]; P=0.11). The median has not yet been reached. Final analysis of OS, performed when 715 deaths have occurred, is anticipated in 2013.

A subgroup analysis of patients at high risk (defined as FIGO III debulked to >1.0 cm or FIGO IV with debulking), performed in an exploratory manner, found that reduction in risk of death in the bevacizumab group was 36.6%; 79 vs. 109 deaths in the standard chemotherapy group (HR 0.64 [0.48–0.85]; P=0.002).

Women tolerated the treatment well without a substantial increase in side effects, the investigators noted, which were generally mild and manageable.

“It's too early to reach firm conclusions about the full extent of the overall survival benefit of adding bevacizumab to the treatment regimen for newly diagnosed ovarian cancer, but it does seem very promising, particularly for patients at high risk of recurrence,” said Dr. Kristensen.