Results of ICON7 trial will influence discussion of treatment options between oncologists and patients.
Early results from the ICON7 trial suggest that adding bevacizumab(Drug information on bevacizumab) (Avastin) to standard chemotherapy in women with newly diagnosed ovarian cancer reduces the risk of disease progression during the first year of treatment.
The findings from the large, multicenter, phase III trial were announced at ESMO 2010 by ICON7 lead investigator Timothy J. Perren, MD, a consultant medical oncologist at Leeds Teaching Hospitals NHS Trust, UK.
Ovarian cancer initially responds very well to surgical treatment and chemotherapy, but the benefit is short lived, Dr. Perren said. "More than half of the patients go on to develop recurrent disease from which they will eventually die, despite our best current treatment," he explained. "For the women we have included in the ICON7 trial, the average time to development of recurrent disease is about 18 months and the average survival time is about three and a half years."
Bevacizumab has been shown to improve outcomes in breast and colon cancer. To see whether it worked in ovarian cancer, the ICON7 investigators randomized 1,528 women (median age, 57 years) with high-risk early- or advanced-stage epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer to one of two treatment regimens after their surgery.
Women in the control arm were randomized to six cycles of standard chemotherapy (carboplatin AUC 6 and paclitaxel(Drug information on paclitaxel) 175 mg/m2) alone given once every three weeks. Women in the research arm of the trial were randomized to the same chemotherapy regimen given concurrently with bevacizumab (7.5 mg/kg) for six cycles, followed by maintenance bevacizumab for 12 additional cycles (abstract LBA4).
At 12 months, the risk of developing further progression of ovarian cancer was reduced by 15% when compared with the risk of progression seen with chemotherapy treatment alone. The effect of bevacizumab was strongest at 12 months, but then fell over time. Overall, the median progression-free survival in the control arm was 17.3 months vs 19 months in the research arm (P = .0041), Dr. Perren reported. Bevacizumab appeared to have a stronger effect in patients with a particularly poor prognosis, he added.
Dr. Perren also noted that the drug was well tolerated by the patients, with high blood pressure as the most common adverse event related to bevacizumab. Eighteen percent of the patients required antihypertensive medication. In comparison, 2% of women in the standard chemotherapy arm developed high blood pressure necessitating treatment.
The results from ICON7 support the findings of the Gynecologic Oncology Group (GOG 218) trial that were announced in June at the 2010 American Society of Clinical Oncology meeting, Dr. Perren said (ASCO abstract LBA1).
"This is the first new drug in first-line treatment since the mid-1990s to show an improvement in outcome for ovarian cancer so it is a very big step forward," he said. "The results of ICON7 and GOG 218 will undoubtedly influence the discussions patients have with their oncologists, but probably more than that, it is going to influence the next generation of clinical trials. It is not possible to ignore these data."