Complete Response to Aflibercept-FOLFIRI in One Patient With Colorectal Cancer Refractory to Bevacizumab-FOLFOX: A Possible Autocrine Vascular Endothelial Growth Factor Receptor 2-Related Mechanism

What is already known about this subject? To date, various antiangiogenic molecules are available in patients with second-line metastatic colorectal cancer with similar clinical benefits. Large prospective clinical trials failed in their attempt to find predictive biomarkers probably because of the tumor heterogeneity, and only a few studies evaluated tumor resistance in a dynamic manner with repeated biopsies. Because of multiple mechanisms of tumor resistance to antiangiogenic molecules, we should focus on outstanding responders to understand their high sensitivity and find the underlying mechanism. Circulating vascular endothelial growth factor receptor 2 (VEGFR2) recently was correlated with response to aflibercept in the VELOUR trial. What are the new findings? We observed in our patient the appearance of tumor VEGFR2 expression at progression in a dynamic manner after bevacizumab exposure. This tumor was highly sensitive to aflibercept-infusional fluorouracil, leucovorin, and irinotecan with a long-lasting complete response. This finding suggests a possible role of autocrine VEGFR2 as a dynamic predictive biomarker. How might it affect clinical practice in the foreseeable future? The possible predictive role of tumor VEGFR2 as bevacizumab resistance and aflibercept sensitivity should be evaluated in a large cohort. Future biomarker studies of antiangiogenic treatments need repeated (tissue or liquid) biopsies and should include tumor VEGFR2.