Robert A. Wolff, MD, Professor in the Department of Gastrointestinal Oncology at The University of Texas MD Anderson Cancer Center, Houston, observed, “The bevacizumab seemed to leverage the capecitabine with a magnitude of benefit that is very reminiscent of the initial trials with irinotecan/5-FU/leucovorin (IFL).” The median duration of survival was 20.3 months in the group given IFL plus bevacizumab, as compared with 15.6 months with IFL plus placebo (HR = 0.66; P < .001), Hurwitz et al reported in 2004.2
“When we use oxaliplatin-containing regimens, we don’t see this leverage. The improvement in progression-free survival is quite modest when bevacizumab is added to a more active cytotoxic backbone,” he said. “Why do you get more leverage with a simpler cytotoxic plus bevacizumab?”
Dr. Cunningham said the answer is unclear, but perhaps pairing bevacizumab with continuous (oral) dosing of the fluoropyrimidine is simply the optimal way to use the drug. He further suggested that the study population may be the optimal group for this combination. “Despite receiving only one line of therapy (only 37% received subsequent treatment),” he noted, overall survival was high even in the control group. “This may be a unique population” with relatively indolent disease, or perhaps the study selected a group for whom this combination is simply effective, he offered.
Earlier Data Confirmed
Jordan Berlin, MD, Ingram Professor of Cancer Research and Clinical Director of the Gastrointestinal Oncology Program at Vanderbilt-Ingram Cancer Center, Nashville, seconded Dr. Wolff’s observations about the Hurwitz data. “This study confirms earlier data that fluoropyrimidine plus bevacizumab does have an interesting effect,” he said. The fact that the capecitabine-alone arm produced a median survival of almost 17 months also confirms previous studies that suggested a subset of patients may be well off without aggressive therapy upfront, “for whom there is a benefit from treating with monotherapy and not necessarily going straight to doublets that are more toxic,” Dr. Berlin said.
He reminded listeners, however, that patients with an abnormal glomerular filtration rate may be at risk for toxicity from capecitabine, which “could be an issue with the elderly.” ■
Disclosure: Dr. Berlin reported no potential conflicts of interest.
