Oct 15, 2010 - 5:10 pm
Bevacizumab Confirmed Beneficial For First-Line Ovarian Cancer Treatment
MILAN (EGMN) - Early findings from the phase III ICON-7 study have shown that bevacizumab added to standard, first-line chemotherapy for advanced epithelial ovarian cancer improves progression-free survival to a greater extent than does standard chemotherapy alone.
Progression-free survival, the primary end point for the trial, was a median of 17.3 months in patients who received standard first-line chemotherapy for ovarian cancer, but 19 months for those who received additional therapy with bevacizumab (hazard ratio, 0.81; log rank P = .0041).
As ICON-7 is the second trial to show such a benefit for bevacizumab (Avastin), these new findings could help Roche to gain approval for using the antiangiogenic agent in the first-line treatment of advanced epithelial ovarian cancer.
The first trial to show a possible benefit of bevacizumab in first-line ovarian cancer treatment was the Gynecologic Oncology Group (GOG)-218 trial (J. Clin. Oncol. 2010 [June 20 suppl.] abstract LBA1), said Dr. Tim J. Perren, a consultant medical oncologist at the St. James's Institute of Oncology in Leeds, England. At the American Society of Clinical Oncology meeting earlier this year, investigators reported a median progression-free survival of 14.1 months with the addition of bevacizumab to standard chemotherapy, compared with 10.3 months in control patients.
"Both trials looked at bevacizumab added to standard chemotherapy as first-line therapy for ovarian cancer," he said in an interview at the annual Congress of the European Society for Medical Oncology. However, whereas ICON-7 used bevacizumab at a dose of 7.5 mg/kg (the dose used in metastatic colorectal cancer), GOG-218 used 15 mg/kg (the dose used in advanced breast cancer). ICON-7 was also a two- rather than three-arm study; it involved patients with both early and advanced disease rather than just stage III/IV, and had a slightly shorter bevacizumab maintenance phase: 12 cycles (36 weeks) rather than up to 22 cycles (66 weeks).
Patient recruitment into the ICON-7 study began in December 2006 and ended in February 2009 at 263 clinical sites, with 1,528 women with newly diagnosed, epithelial ovarian, primary, or fallopian tube cancer evenly randomized to treatment with paclitaxel (175 mg/m²) plus carboplatin (area under the curve = 6.0) given in six 21-day cycles with or without additional bevacizumab. Bevacizumab (7.5 mg/kg) was given during the chemotherapy, and continued in the experimental arm as maintenance therapy.
At a median follow-up of 19.4 months, two patients were still on treatment, and there had been 759 cases of disease progression or death, including 241 deaths - 16% of the 715 required for final outcome analysis.
An exploratory analysis of women who had FIGO stage III disease with suboptimal debulking and those who had stage IV disease with debulking showed an even greater difference in progression-free survival in favor of bevacizumab (15.9 vs. 10.5 months; HR, 0.68; P = .001).
"The biggest clinically significant effect we saw was hypertension," Dr. Perren said, noting that this occurred in 25.9% of patients in the bevacizumab arm and 6.2% of the control arm, and that 18% and 2%, respectively, in each group required treatment with antihypertensives. Other well-known side effects of antiangiogenics and the chemotherapeutic agents used were also seen, including bleeding (39.6% vs. 11.6%) and neutropenia (28.3% vs. 29.1%).
"Bevacizumab undoubtedly has activity in ovarian cancer," Dr. Perren said. "It's a drug that we don't fully know how to use yet and exactly which patients are going to benefit from it, but it will be central to future research trials in ovarian cancer."
"ICON-7 validated and extends the observations of GOG-218," said Dr. Michael A. Bookman, chief of the hematology-oncology section of the Arizona Cancer Center in Tucson, and an investigator of the GOG-218 trial.
"The improvement in progression-free survival has not yet been accompanied by improvements in overall survival and that does raise questions about the true clinical benefit," Dr. Bookman observed. While there is still research to be done with bevacizumab in the first-line setting, he said that "there is no question that bevacizumab achieves clinical benefit in patients with recurrent disease."
ICON-7 was a Gynaecologic Cancer Intergroup (GCIG) trial run through the U.K. Medical Research Council's Clinical Trials Unit. Roche provided bevacizumab and grants to perform the ICON-7 study. Dr. Perren has accepted travel and accommodation costs but not consultancy fees to attend Roche-sponsored advisory boards. Dr. Bookman had no financial interests to disclose but has acted as an ad hoc advisor to various pharmaceutical companies and was also a GOG-218 trial investigator.