BETHESDA, MarylandData from the randomized, phase III E3200
trial show that patients with advanced colorectal cancer who were treated with
bevacizumab (Avastin) in combination with the oxaliplatin (Eloxatin)-based
regimen known as FOLFOX4 had a significant survival advantage, compared with
patients treated with FOLFOX4 alone. The National Cancer Institute (NCI)
released the results from an interim analysis at the recommendation of the
trial’s data monitoring committee (DMC), after the trial monitors determined
that the study had met its primary endpoint of improved overall survival.
Patients treated with bevacizumab and FOLFOX4 (oxaliplatin,
fluorouracil, and leucovorin) had a median overall survival of 12.5 months vs
10.7 months for those receiving FOXFOX4 alone. The difference represented a 17%
improvement in median overall survival and a 26% reduction in the risk of death
for the bevacizumab arm.
"We now know that bevacizumab added to second-line
chemotherapy with FOLFOX4 improves survival," said study chair Bruce J.
Giantonio, MD, of the University of Pennsylvania’s Abramson Cancer Center.
"With these findings, we can now more confidently expect survival for people
with advanced disease to be more than double what it was just a few years ago."
Dr. Giantonio said that preliminary results of the E3200 trial will be
presented at the American Society of Clinical Oncology’s Gastrointestinal
Cancers Symposium this month.
Bevacizumab binds to and inhibits vascular endothelial
growth factor (VEGF), a crucial player in tumor angiogenesis. Oxaliplatin is a
novel platinum-based anticancer drug that destroys cancer cells. "The results
of this study are very important for all those living with advanced colorectal
cancer," said NCI director Andrew C. von Eschenbach, MD. "They provide further
confirmation that a biologic agent that targets a tumor’s blood supply can
prolong survival when combined with chemotherapy, even for patients who have
previously received therapy for advanced disease."
NCI sponsored the 829-patient trial, which was conducted by
a network of researchers led by the Eastern Cooperative Oncology Group. Accrual
occurred between October 2001 and April 2003. Investigators accepted advanced
colorec-tal patients previously treated with a fluorouracil-based therapy and
irinotecan (Camptosar), alone or at the same time, who had advanced disease or
a relapse within 6 months of adjuvant treatment.
Patients were randomized to three groups: FOLFOX4 plus bevacizumab, standard
FOLFOX4 treatment only, or bevacizumab only. In March 2003, trial investigators
stopped randomizing patients to the bevacizumab-only arm after the DMC found
that early data indicated this group of patients might have a lower overall
survival than those in the other two arms. The treatment toxicities associated
with bevacizumab were consistent with previous trials in which the drug was
combined with chemotherapy.
