Predictive Biomarker for Bevacizumab May Be Emerging

December 2011, Vol 2, No 7

Stockholm, Sweden—Investigators appear to be closer to identifying a biomarker that may predict response to bevacizumab (Avastin).

At the European Society for Medical Oncology’s 2011 European Multidisciplinary Cancer Congress, several presentations focused on baseline levels of a short isoform of the vascular endothelial growth factor (VEGF), plasma (p) VEGF-A. Thanks to a novel, highly sensitive enzyme-linked immunosorbent assay, this can now be measured.

Investigators analyzed blood samples from 6 randomized trials in various tumor types and correlated pVEGF-A with clinical outcomes. Median baseline levels of several candidate biomarkers were prespecified as a cut point to categorize patients as being low or high in pVEGF-A.

“Of several putative predictive biomarkers for bevacizumab, pVEGF-A is a lead candidate,” said Gordon C. Jayson, PhD, of the University of Manchester, United Kingdom.

The analysis showed that baseline pVEGF-A is potentially predictive (for response to therapy) and prognostic (for outcome, regardless of treatment) in metastatic breast, gastric, and pancreatic cancers, based on findings from the pivotal AVADO, AVAGAST, and AVITA trials, respectively.

In AVADO, progression-free survival was greatest for metastatic breast cancer patients with high pVEGF-A receiving bevacizumab (hazard ratio [HR], 0.49; P = .08); the marker was prognostic for overall survival (OS) in AVADO.

In AVAGAST, the OS was greatest for patients with metastatic gastric cancer and high pVEGF-A receiving bevacizumab (HR, 0.72; P = .07).

Similarly, in AVAIL, high baseline pVEGF-A correlated with worse OS in the placebo arm, but treatment with bevacizumab improved outcomes enough to put patients on par with those who had low baseline pVEGF-A (P = .03).

But pVEGF-A is prognostic only (not predictive) in metastatic colorectal cancer, non–small-cell lung cancer, and renal-cell carcinoma based on the AVF2107g, AVAIL, and AVOREN trials, respectively.

It is unclear why the biomarker is robust in some tumor types but not in others. The difference in its predictive potential may be a reflection of variations in sample handling among these trials, Dr Jayson suggested, “although we cannot exclude a true negative in colorectal, non–small-cell lung cancer, and renal cancer.”

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