The need for further study of bevacizumab in gastric cancer in the West is debatable, according to Dr. Ilson, also of the Memorial Sloan-Kettering Cancer Center. "And I think an even bigger and overarching question is, Are agents targeting only one pathway really worth investigating? Should we be looking at multitargeted agents," or combining agents?
Dr. David H. Ilson
"The holy grail here, which never gets enough mention, is that we need to identify and validate biomarkers to direct therapy to the appropriate patient," he said.
In the unplanned, exploratory analysis, Dr. Shah and his team found that among patients from Europe and the Americas, the addition of bevacizumab improved overall survival significantly for those having diffuse disease (hazard ratio, 0.68) and marginally for those having distal disease (0.72). When these two groups were combined, the risk of death was reduced by one-third (0.67).
In an analysis of potential biomarkers of bevacizumab efficacy, survival benefit differed by tumor NRP-1 level (P = .06) – with only patients having below-median levels deriving benefit – and by plasma VEGF-A level (P = .07) – with only patients having above-median values deriving benefit.
Proximal tumors generally had higher tumor NRP-1 levels and lower plasma VEGF-A levels. By comparison, diffuse tumors had relatively low NRP-1 levels, and distal tumors had relatively high plasma VEGF-A levels.
"There is heterogeneity with these biomarkers across the different subtypes, and this is in support of the concept that subtypes are clinically meaningful," Dr. Shah commented. "Proximal tumors tend to have the worst profile, if you will, for bevacizumab."
Dr. Shah reported that he is a consultant to Genentech. Dr. Ilson reported that he receives research funding from Bayer, BMS-Imclone, Roche-Genentech, and Sanofi-Aventis.