Cetuximab, brivanib failed to extend OS in metastatic colorectal carcinoma
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.
Herbert Hurwitz, MD
Associate professor of medicine
Duke University Medical Center
Disclosure: Dr. Hurwitz reports receiving research funding from Genentech/Roche.