CHICAGO —Serum levels of carbonic anhydrase IV (sCAIX) were associated with improved pathologic complete response rates in patients with primary breast cancer who were receiving bevacizumab, in cases where bevacizumab did not confer benefit in patients with high sCAIX levels, a study presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting has shown.1

In the GeparQuinto phase 3 study, 1948 patients with HER2-negative tumors were randomly assigned to receive epirubicin plus cyclophospamide, followed by docetaxel with or without 8 infusions of bevacizumab, every 3 weeks prior to surgery. Patients without clinical response were then randomly assigned to 12 weekly cycles of paclitaxel with or without everolimus.

Serum samples were taken at baseline and at 2 additional time points from 39% of patients treated with bevacizumab and from 38% of those treated without it. By using Enzyme-linked immunosorbent assay, researchers determined pre-treatment serum sCAIX levels, and then assessed correlations between sCAIX levels and pathologic complete response, disease-free survival, and overall survival.

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Eleven hundred eighty-nine patients with HER2-negative breast cancer, of which 577 received bevacizumab, were analyzed. Results showed sCAIX levels were elevated upon addition of 4 cycles of bevacizumab to neoadjuvant chemotherapy.

“The addition of bevacizumab to neoadjuvant chemotherapy induced an increase of sCAIX,” said lead investigator Melanie Janning, MD, MSc, of the University Medical Center Hamburg-Eppendorf in Hamburg, Germany.

Researchers found that patients with low baseline sCAIX levels, who were treated with neoadjuvant chemotherapy alone, had a lower likelihood of achieving a pathologic complete response, in contrast with those who displayed higher sCAIX levels (P = .007).

Subgroup analyses demonstrated that among patients with hormone receptor-negative tumors and low baseline sCAIX levels, those treated with neoadjuvant chemotherapy alone were more likely to have a pathologic complete response than those who received chemotherapy plus bevacizumab (P = .002).

Disease-free survival was significantly improved in patients with higher sCAIX levels when they were treated with neoadjuvant chemotherapy alone in contrast to chemoimmunotherapy-treated patients overall (P = .033) and in those with hormone receptor-positive tumors (P = .028). sCAIX levels, however, were not associated with overall survival.

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“Patients with low sCAIX levels at baseline were less likely to achieve a pathologic complete response and displayedworse disease-free survival when treated with neoadjuvant chemotherapy alone,” Dr Janning concluded. “Patients with low sCAIX levels at baseline had a higher chance to achieve pathologic complete response when bevacizumab was added.”                       


  1. Janning M, Muller V, Vettorazzi E, Cubas-Cordova M, Eulenburg C, Schem C, et al. Serum carbonic anhydrase IX as predictive marker for efficacy of bevacizumab: A biomarker analysis from the GeparQuinto phase III neoadjuvant breast cancer trial. J Clin Oncol. 2016; 34 (suppl; abstr 11505).