In elderly patients with treatment-naive metastatic colorectal cancer, a trend toward a survival benefit was observed for bevacizumab (Avastin) plus capecitabine (Xeloda) in the international phase III AVEX trial, which was presented at the 2013 Gastrointestinal Cancers Symposium by David Cunningham, MD, Consultant Medical Oncologist and Head of the Gastrointestinal Unit at the Royal Marsden Hospital, London.1
Although bevacizumab is a standard of care in metastatic colorectal cancer, AVEX is the first phase III trial to prospectively evaluate the use of the drug—or any biologic—in an elderly colorectal cancer population, “a population that is in general undertreated,” Dr. Cunningham said.
Study Details
The study enrolled 280 treatment-naive patients aged ≥ 70 (mean age 76) across 10 countries. As first-line treatment for metastatic disease, patients were randomly assigned to receive 7.5 mg/kg bevacizumab every 3 weeks and 1,000 mg/m2 capecitabine twice a day on days 1 to 14, or 1,000 mg/m2 capecitabine alone twice a day on days 1 to 14.
The addition of bevacizumab to capecitabine significantly improved progression-free and overall survival. Progression-free survival was 9.1 months with the combination vs 5.1 months without (HR = 0.53; P < .001), which was consistent across all subgroups. The objective response rate was doubled, from 10.0% to 19.3% (P = .042), and the disease control rate was 74.3% with the combination vs 57.9% with monotherapy (P = .005). A numerically longer overall survival was observed with bevacizumab—20.7 months vs 16.8 months—but this did not reach statistical significance (HR = 0.79; P = .182), Dr. Cunningham said.
“Most people looking at the curve would be impressed by the trend favoring the combination, and a median survival of 20.7 months,” he commented. “Given the type of patients recruited, this is a worthwhile endeavor for the patients who receive it.”
The study was powered to show a difference in progression-free but not overall survival, the authors noted.
Adverse Events Similar between Groups
The combination group had greater study drug exposure, receiving a median of 5.8 cycles, vs 4.2 in the capecitabine arm. In spite of this, rates of any adverse event were similar between the groups, 95%. Grade 3 or 4 adverse events were more common with the combination than the single agent (59% vs 44.1%), but grade 5 adverse events were more common in patients receiving only capecitabine (11.8% vs 8.2%).
Dr. Cunningham suggested that this high rate of grade 5 toxicity “probably reflects the population being treated, whose average age was 76.”
Adverse events of special interest with bevacizumab included bleeding/hemorrhage, which occurred in 25.4% of patients vs 6.6% with capecitabine, though grade 3 and higher toxicities were similar. Hypertension was more common in the combination group, but grade 3 and higher was observed in only 2.2%, vs 1.5% with capecitabine. Venous and atrial thromboembolisms were also more common but grade 3 and higher events were rare.
“The safety profile was consistent with previously reported data for bevacizumab in colorectal cancer,” he noted. “The combination is clearly effective, generally well tolerated, and in those over 70 results in meaningful disease control and good survival,” Dr. Cunningham maintained. “This is an international study, so the findings can be widely extrapolated.” ■
Disclosure: Dr. Cunningham has received research funding from AstraZeneca, Merck, and Roche.
References
1. Cunningham D, Lang I, Lorusso V, et al: Bevacizumab in combination with capecitabine for the first-line treatment of elderly patients with metastatic colorectal cancer. 2013 Gastrointestinal Cancers Symposium. Abstract 337. Presented January 26, 2013.
2. Hurwitz H, Fehrenbacher L, Novotny W, et al: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335-2342, 2004.
