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

Journal article


Publication Details

Author(s): Janning M, Müller V, Vettorazzi E, Cubas-Cordova M, Gensch V, Ben-Batalla I, zu Eulenburg C, Schem C, Fasching P, 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
Journal: International Journal of Cancer
Publication year: 2019
ISSN: 0020-7136


Abstract

We analyzed the predictive potential of pretreatment soluble carbonic anhydrase IX levels (sCAIX) for the efficacy of bevacizumab in the phase III neoadjuvant GeparQuinto trial. sCAIX was determined by enzyme-linked immunosorbent assay (ELISA). Correlations between sCAIX and pathological complete response (pCR), disease-free and overall survival (DFS, OS) were assessed with logistic and Cox proportional hazard regression models using bootstrapping for robust estimates and internal validation. 1,160 HER2-negative patient sera were analyzed, of whom 577 received bevacizumab. Patients with low pretreatment sCAIX had decreased pCR rates (12.1 vs. 20.1%, p = 0.012) and poorer DFS (adjusted 5-year DFS 71.4 vs. 80.5 months, p = 0.010) compared to patients with high sCAIX when treated with neoadjuvant chemotherapy (NCT). For patients with low sCAIX, pCR rates significantly improved upon addition of bevacizumab to NCT (12.1 vs. 20.4%; p = 0.017), which was not the case in patients with high sCAIX (20.1% for NCT vs. 17.0% for NCT-B, p = 0.913). When analyzing DFS we found that bevacizumab improved 5-year DFS for patients with low sCAIX numerically but not significantly (71.4 vs. 78.5 months; log rank 0.234). In contrast, addition of bevacizumab worsened 5-year DFS for patients with high sCAIX (81 vs. 73.6 months, log-rank 0.025). By assessing sCAIX levels we identified a patient cohort in breast cancer that is potentially undertreated with NCT alone. Bevacizumab improved pCR rates in this group, suggesting sCAIX is a predictive biomarker for bevacizumab with regards to treatment response. Our data also show that bevacizumab is not beneficial in patients with high sCAIX.


FAU Authors / FAU Editors

Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe


External institutions with authors

Deutsches Herzzentrum Berlin
Frankfurt Cancer Institute
GBG Forschungs GmbH (German Breast Group)
Heinrich-Heine-Universität Düsseldorf
HELIOS Kliniken
Klinikum Chemnitz
Klinikum der Universität München
OncoConsult
Onkologische Schwerpunktpraxis Bielefeld
Städtische Kliniken Esslingen
St. Barbara-Klinik Hamm
Universitätsklinikum Hamburg-Eppendorf
Universitätsklinikum Schleswig-Holstein (UKSH)
Verein zur Förderung der Senologie/Brustklinik e.V.


How to cite

APA:
Janning, M., Müller, V., Vettorazzi, E., Cubas-Cordova, M., Gensch, V., Ben-Batalla, I.,... Loges, S. (2019). 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. International Journal of Cancer. https://dx.doi.org/10.1002/ijc.32163

MLA:
Janning, Melanie, et al. "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." International Journal of Cancer (2019).

BibTeX: 

Last updated on 2019-14-05 at 16:53