NO BENEFIT OF BRIVANIB FOR COLORECTAL CANCER 

NEW YORK (Reuters Health) May 28 - Adding brivanib to cetuximab doesn't improve survival with refractory metastatic colon cancer, but it increases adverse events, a new study shows.

"Although this targeted combination of brivanib plus cetuximab improved objective response and progression-free survival in patients with advanced, chemotherapy-refractory, wild-type KRAS colorectal cancer, the study did not meet its primary endpoint of overall survival, and the combination was associated with increased toxicity," Dr. Lillian L. Siu of Princess Margaret Hospital, Toronto told Reuters Health by email.

Cetuximab, an antiepidermal growth factor receptor monoclonal antibody, has already improved survival in this setting. Brivanib, a tyrosine kinase inhibitor targeting receptors for vascular endothelial and fibroblast growth factors, has looked promising, according to a May 20th online paper in the Journal of Clinical Oncology by Dr Siu and colleagues.

To evaluate the combination, the investigators randomized 750 patients to receive IV cetuximab with or without oral brivanib. Everyone in the study had already received combination chemotherapy with fluorouracil or capecitabine, as well as irinotecan and oxaliplatin, or had contraindications to those drugs, and had disease progression within six months.

On intent-to-treat analysis, the median progression-free survival was 5.0 months in the active combination group and 3.4 months in the placebo group. There also were significantly more partial responses in combination patients (13.6% vs 7.2%).

Median survival, however, was 8.8 months in combination patients and 8.1 months with placebo. Corresponding one-year survival rates were 35.8% and 30.9%.

Combination patients also had a significantly higher rate of grade 3 or more adverse events (78% vs 53%).

Although it failed to meet the primary endpoint, the study may still yield helpful information, Dr. Siu believes.

"We have collected plasma and tumor biospecimens from a large proportion of patients enrolled in this study and active analyses are ongoing to gain insight on biomarkers that may help predict sensitivity or resistance to angiogenic inhibitors such as brivanib," she said.

SOURCE: http://bit.ly/19jzmH9

J Clin Oncol 2013.