Promising results were recently presented from VELOUR, a second-line phase III trial comparing FOLFIRI (leucovorin, fluorouracil, irinotecan) with vs without aflibercept, a fusion protein that binds placental growth factor, VEGFA, and VEGFB.1 “This is an important trial because it might lead to the approval of a novel agent for colorectal cancer,” said Dr. Grothey.
VELOUR Results
The 1,226 patients enrolled had all experienced failure of oxaliplatin-based therapy. The rate of adverse events leading to treatment discontinuation was about twice as high with aflibercept as with placebo (26.6% vs 12.1%). In addition to the usual anti-VEGF therapy adverse effects such as hypertension, patients had more diarrhea and neutropenia.
With a median follow-up of 22.3 months, the aflibercept group had better progression-free survival (6.9 vs 4.67 months; HR = 0.758; P = .00007) and overall survival (13.5 vs 12.06 months; HR = 0.817; P = .0032).
“The survival curves…split early, they stay separate, and there is clearly survival benefit, although it’s perhaps not as strong as we would like it to be,” Dr. Grothey commented.
In subgroup analyses, benefit appeared greater in patients who were bevacizumab (Avastin)-naive than in those who had received bevacizumab.
Similar Trial
In the similar E3200 Intergroup trial, which tested second-line FOLFOX4 with vs without bevacizumab, all of the patients were bevacizumab-naive, compared with 70% in the VELOUR trial.
“When you compare outcome parameters—overall survival, progression-free survival, and response rates—side by side, they seem to be very similar,” he said, while acknowledging the pitfalls of cross-trial comparisons. Aflibercept is “probably not as new as we would like it to be, particularly since 70% of these patients did not have bevacizumab first line. But it will be interesting to see how this plays out.” ■
Reference
1. Van Cutsem E, Tabernero J, Lakomy R, et al. Intravenous (IV) aflibercept versus placebo in combination with irinotecan/5-FU (FOLFIRI) for second-line treatment of metastatic colorectal cancer (MCRC): Results of a multinational phase 3 trial (EFC10262-VELOUR). 13th ESMO World Congress on Gastrointestinal Cancer. Abstract 0-0024. Presented June 25, 2011.
Colorectal cancer studies reported at this year’s ASCO meeting offered little in the way of practice-changing information, according to Axel Grothey, MD, of the Mayo Clinic in Rochester, Minnesota. But they did confirm existing standards of care, he noted at the Best of ASCO® meeting in Seattle.