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Int J Cancer. 2019 Jan 29. doi: 10.1002/ijc.32163. [Epub ahead of print]

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.

Author information

1
Department of Oncology, Hematology and Bone Marrow Transplantation with section Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
2
Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
3
Clinic and Policlinic for Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
4
Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
5
Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Kiel, Germany.
6
Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
7
Department of Obstetrics and Gynecology, School of Medicine, Johann Wolfgang Goethe-University, Frankfurt, Germany.
8
Department of Gynecology and Obstetrics, University Düsseldorf, Germany.
9
Onkologische Schwerpunktpraxis Bielefeld, Bielefeld, Germany.
10
Department of Gynecology and Obstetrics, Klinikum Esslingen, Esslingen, Germany.
11
Department of Gynecology and Obstetrics, St. Barbara Kliniken Heessen, Hamm, Germany.
12
OncoConsult Hamburg GmbH, Hamburg, Germany.
13
Department of Gynecology and Obstetrics, Klinikum Chemnitz, Germany.
14
Department of Obstetrics and Gynecology, Campus Innenstadt, University Hospital Munich, Germany.
15
Department of Pathology, Charité Berlin Campus Mitte and German Cancer Consortium (DKTK), Berlin, Germany.
16
Department of Gynecology and Obstetrics, Helios Klinikum Berlin-Buch, Berlin, Germany.
17
Centre for Hematology and Oncology, Frankfurt, Germany.
18
Centre for Breast Cancer, Luisenkrankenhaus Düsseldorf, Germany.
19
Breast Cancer Day Clinic, Berlin, Germany.
20
German Breast Group, Neu-Isenburg, Germany.

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.

KEYWORDS:

bevacizumab; breast cancer; carbonic anhydrase IX; neoadjuvant treatment; predictive biomarker

PMID:
30694523
DOI:
10.1002/ijc.32163

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