2012 Gastrointestinal Cancers Symposium
SAN FRANCISCO — Despite improvements in PFS and objective response, the combination of cetuximab and brivanib alaninate did not improve survival for patients with metastatic, refractory wild-type KRAS colorectal carcinoma, according to phase 3 results from the AGITG CO.20 trial.
Median OS was 8.8 months for patients randomly assigned to the combination vs. 8.1 months for patients assigned to cetuximab (Erbitux; Bristol-Myers Squibb, Eli Lily) plus placebo (HR=0.88; 95% CI, 0.74-1.03).
“The primary endpoint of improvement in overall survival was not met,” said Lillian L. Siu, MD, FRCPC, a staff physician at Princess Margaret Hospital and a professor medicine at the University of Toronto.
Patients were randomly assigned to a loading dose of 400 mg/m2 IV cetuximab, followed by a weekly maintenance dose of 250 mg/m2 plus either 800 mg brivanib alaninate daily (n=376) or placebo (n=374). The study took place from February 2008 to February 2011. Eligible patients could receive up to one prior anti-VEGF therapy but could not have received prior anti-EGFR therapy.
Men made up 64% of the population; 92% of patients had undergone three or more previous therapies; and 97% of patients were positive for wild-type KRAS mutation.
Median PFS favored the combination arm, 5 months vs. 3.4 months (HR=0.72; 95% CI, 0.62-0.84). Outcomes also were superior with the combination for partial response (13.6% vs. 7.2%) and stable disease (50% vs. 44%).
However, the combination also was associated with a greater incidence of grade-3 or higher adverse events, 78% vs. 53%. The most common grade-3 or higher adverse events in the combination arm were fatigue (25%), hypertension (11%) and rash (10%). The most common grade-3 or higher adverse events in the placebo arm were fatigue (11%), rash (5%) and dyspnea (5%).
Global quality-of-life scores were lower, and time to deterioration of physical function was shorter in the combination arm, Siu said.
For more information:
- Siu LL. Abstract #386. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 19-21, 2012; San Francisco.
Disclosure: Dr. Siu reports receiving research funding from Bristol-Myers Squibb.
The role of [basic fibroblast growth factor], which has been suggested on multiple preclinical models and from small clinical pilot data, needs to be questioned. Although this does not exclude the benefit, we need to rethink exactly what is the role, particularly given the diagnostic difficulty of assessing [basic fibroblast growth factor] in both plasma and in tissue.
Herbert Hurwitz, MD
Associate professor of medicine
Duke University Medical Center
Disclosure: Dr. Hurwitz reports receiving research funding from Genentech/Roche.