Dr. Josep Tabernero of the Vall D'Hebron University Hospital in Barcelona presented the positive results of the VELOUR study on Sunday September 25, including the newly presented pre-specified subgroup analysis. The primary endpoint results had been reported at the ESMO/WCGC meeting earlier this year.
The trial randomized 1200 metastatic colorectal cancer (mCRC) patients 1:1 to aflibercept plus FOLFIRI or placebo plus FOLFIRI. Patients could have had prior bevacizumab (Avastin) treatment and had been previously treated with oxaliplatin. The overall survival was 13.5 months in the experimental arm compared to 12.06 months in the control arm. The reduction in the risk of dying from mCRC was 18.3% (HR = 0.817, P = .0032).
"The VELOUR study is a positive study. The response rate was almost double," Dr. Tabernero said during his presentation. "There were no interactions in patients with or without prior bevacizumab and no signs of interaction of the drug with a history of hypertension," he stated. Efficacy results were consistent for all subgroups analyzed (age, gender, race, prior hypertension, number of organ metastases, liver metastases, and primary cancer location). There was no difference between grade 3 and 4 adverse events in the two study arms.
Currently, the decision of a second-line treatment is based on the previous first-line treatment and the patient's comorbidities and toxicity tolerances. According to the discussant, Dr. David Kerr of the University of Oxford, FOLFOX and bevacizumab are superior in the second-line setting in terms of progression-free survival and overall survival compared to FOLFOX after failure on irinotecan (Camptosar). For patients who are wild-type for the KRAS mutation and have not been previously treated with anti-EGFR antibodies, other options include cetuximab (Erbitux) with or without irinotecan, or panitumumab with or without FOLFIRI. Dr. Kerr believes that the landscape has changed based on the results of the VELOUR study and that this agent should be considered for those patients who progress after first-line treatment with FOLFOX with or without bevacizumab. New ESMO guidelines for MRCR will be issued soon. Dr. Kerr ended by saying, "It is a beautifully designed and run study, but we would like to collect more data."
Aflibercept is a novel anti-VEGF/PIGF fusion protein consisting of the two key domains of the human VEGF 1 and 2 proteins. It is currently in clinical trials for lung cancer, melanoma, lymphoma, and ovarian cancer as part of different combination regimens.