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Evaluation of sCAIX as predictive marker for efficacy of neoadjuvant bevacizumab


A translational research study performed with samples obtained from a cohort of patients with HER2-negative breast cancer enrolled in the neoadjuvant GeparQuinto (GBG 44) trial has been published in the International Journey of Cancer.

Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A), improves the pathological complete response (pCR) rates but not long-term outcome in patients eligible for neoadjuvant treatment. To date, efficient biomarkers for the selection of patients who may benefit from the addition of bevacizumab to neoadjuvant chemotherapy is missing. Therefore, the primary aim of this biomarker study was to evaluate the potential of plasma soluble carbonic anhydrase IX (sCAIX) levels to predict the pCR in patients with locally advanced, HER2-negative breast cancer from GeparQuinto trial. The GeparQuinto study demonstrated improved pCR rates from 14.9% to 18.4% (OR=1.29 [95%CI 1.02-1.65]; p=0.04) upon the addition of bevacizumab to neoadjuvant chemotherapy. Serum samples from 1160 patients with HER2-negative breast cancer treated with bevacizumab plus neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone were analyzed. The predictive potential of sCAIX levels for disease-free survival (DFS) and overall survival (OS) were also assessed. The results showed that patients with pre-treatment low sCAIX levels treated with standard neoadjuvant therapy were less likely to achieve a pCR and had a worse DFS compared to those with high sCAIX levels. The addition of bevacizumab improved outcome for patients with low sCAIX while it was not beneficial for patients with high sCAIX levels. For patients with low sCAIX levels the bevacizumab effect was only statistically significant with respect to pCR but not to DFS. However, these findings demonstrated that treatment intensification warrants exploration in early breast cancer patients with low sCAIX levels.

Janning M, Müller V, Vettorazzi E, Cubas-Cordova M, Gensch V, Ben-Batalla I, Zu Eulenburg C, Schem C, Fasching PA, Schnappauf B, Karn T, Fehm T, Just M, Kühn T, Holms F, Overkamp F, Krabisch P, Rack B, Denkert C, Untch M, Tesch H, Rezai M, Kittel K, Pantel K, Bokemeyer C, Loibl S, von Minckwitz G, Loges S. Evaluation of soluble carbonic anhydrase IX as predictive marker for efficacy of bevacizumab: a biomarker analysis from the GeparQuinto phase III neoadjuvant breast cancer trial. Int J Cancer. 2019 Jan 29 [Epub ahead of print].
Link in PubMed


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