Bevacizumab Benefits Patients Who Are Not Candidates for First-Line Irinotecan

LOS ANGELES-Bevacizumab (Avastin) plus fluorouracil(Drug information on fluorouracil) (5- FU)/leucovorin (LV) can improve outcomes in patients with metastatic colorectal cancer who are not candidates for initial therapy with irinotecan(Drug information on irinotecan) (CPT-11, Camptosar), according to results of a phase II trial (abstract 3516). "Avastin, when combined with chemotherapy in these patients with metastatic colorectal cancer, improves survival and improves response rates," said lead investigator Fairooz F. Kabbinavar, MD, associate professor of medicine, University of California, Los Angeles. "This improvement in efficacy was not associated with an increase in toxicity." The patients were randomized to receive the Roswell Park 5-FU/LV regimen with or without bevacizumab(Drug information on bevacizumab) 5 mg/kg IV every 2 weeks. Adding bevacizumab significantly prolonged median progression-free survival time by nearly 4 months and there was a trend toward improved response rate, duration of response, and survival. Notably, there was a significant survival benefit reported for patients who had low serum albumin at study entry. Elderly Population
"The study looks at patients who are elderly, who have lost a little bit of weight, who are not 100% functional, who may have received prior radiation- patients who would not be able to tolerate a full-dose regular chemotherapy combination," Dr. Kabbinavar said. "For them, it's a very effective alternative regimen." A total of 209 patients received either 5-FU/LV/bevacizumab or 5-FU/ leucovorin/placebo. Patients were eligible for the study if they were judged as not optimal candidates for irinotecan- based therapy and had one of the following risk factors at baseline: age 65 years or older, Eastern Cooperative Oncology Group (ECOG) performance status 1 or 2, serum albumin of 3.5 g/dL or less, or prior radiotherapy to the pelvis or abdomen. Survival Benefit
Progression-free survival time in the bevacizumab-treated patient group was 9.2 months vs 5.5 months in the placebo arm (hazard ratio [HR]= 0.50, P = .0002). There was a trend toward improved median survival time in the bevacizumab arm, 16.6 months vs 12.9 months for placebo arm (HR = 0.79, P = .16). The response rate was also somewhat higher in the bevacizumab arm, 26% vs 15.2% for placebo ( P = .55). Low serum albumin at baseline was associated with a significant survival benefit. Patients with serum albumin of 3.5 g/dL or lower had a median survival time of 15.3 months in the bevacizumab arm and 7.5 months in the placebo arm (HR= 0.46, P = .001). Otherwise, results by baseline risk factors were "generally consistent" with the overall results, investigators said. At 60 days, all-cause mortality was higher in the placebo group, 13.5% vs 5% in the bevacizumab group. Grade 3 hypertension was increased in the bevacizumab group but was readily managed with medication, investigators said. The safety data also included reports of two cases of gastrointestinal perforation (2%) in the bevacizumab arm, consistent with what has been found in previous investigations (see Table 1). Strengthening the Evidence
This trial reported by Dr. Kabbinavar was a smaller companion trial to the larger phase III trial (N Engl J Med 350(23):2335-2342, 2004) showing that bevacizumab prolongs survival when added to irinotecan/5-FU/LV (IFL). Reported median survival time in the larger trial was 15.6 months for IFL alone, and 20.3 months for IFL plus bevacizumab ( P < .001). "Together with the larger phase III trial results...these data strengthen the evidence that bevacizumab-based therapy should be a standard option for the initial treatment of metastatic colorectal cancer," the investigators concluded.