Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients
with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group
B (CALGB 80303).
Author(s): Kindler HL, Niedzwiecki D, Hollis D, Sutherland S, Schrag D, Hurwitz H, Innocenti
F, Mulcahy MF, O'Reilly E, Wozniak TF, Picus J, Bhargava P, Mayer RJ, Schilsky
RL, Goldberg RM.
Affiliation(s): University of Chicago Cancer Research Center, Chicago, IL 60637-1470, USA.
hkindler@medicine.bsd.uchicago.edu
Publication date & source: 2010, J Clin Oncol. , 28(22):3617-22
PURPOSE: The combination of gemcitabine plus bevacizumab produced a 21% response
rate and a median survival of 8.8 months in a multicenter phase II trial in
patients with metastatic pancreatic cancer. These encouraging data led Cancer and
Leukemia Group B (CALGB) to conduct a double-blind, placebo-controlled,
randomized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo
in advanced pancreatic cancer patients.
PATIENTS AND METHODS: Eligible patients had no prior therapy for advanced
disease, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, no
tumor invasion of adjacent organs, and no increased bleeding risk. The primary
end point was overall survival. Patients were stratified by performance status,
extent of disease, and prior radiotherapy. Patients received gemcitabine at 1,000
mg/m(2) over 30 minutes on days 1, 8, and 15 every 28 days and bevacizumab at 10
mg/kg or placebo on days 1 and 15 every 28 days.
RESULTS: Between June 2004 and April 2006, 602 patients were enrolled onto the
study and 535 were treated. Median overall survival was 5.8 months for
gemcitabine/bevacizumab and 5.9 months for gemcitabine/placebo (P = .95). Median
progression-free survival was 3.8 and 2.9 months, respectively (P = .07). Overall
response rates were 13% and 10%, respectively. Patients with a performance status
of 0, 1, and 2 survived a median of 7.9, 4.8, and 2.4 months, respectively. The
only statistically significant differences in grades 3 and 4 toxicity occurred
for hypertension (10% v 3%; P < .001) and proteinuria (5% v 1%; P = .002); venous
thrombosis grade > or = 3 was equivalent in both arms (14% and 15%,
respectively).
CONCLUSION: The addition of bevacizumab to gemcitabine does not improve survival
in advanced pancreatic cancer patients.
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