Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant

Pauline Wimberger, Mara Julia Gerber, Jacobus Pfisterer, Kati Erdmann, Susanne Füssel, Theresa Link, Andreas Du Bois, Stefan Kommoss, Florian Heitz, Jalid Sehouli, Rainer Kimmig, Nikolaus De Gregorio, Barbara Schmalfeldt, Tjoung Won Park-Simon, Klaus Baumann, Felix Hilpert, Marcel Grube, Willibald Schröder, Alexander Burges, Antje BelauLars Hanker, Jan Dominik Kuhlmann

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Purpose: The identification of a robust IHC marker to predict the response to antiangiogenic bevacizumab in ovarian cancer is of high clinical interest. VEGF-A, the molecular target of bevacizumab, is expressed as multiple isoforms with pro- or antiangiogenic properties, of which VEGF-A165b is the most dominant antiangiogenic isoform. The balance of VEGF-A isoforms is closely related to the angiogenic capacity of a tumor and may define its vulnerability to antiangiogenic therapy. We investigated whether the expression of VEGF-A165b could be related to the effect of bevacizumab in advanced ovarian cancer patients. Experimental Design: Formalin-fixed paraffin-embedded tissues from 413 patients of the ICON7 multicenter phase III trial, treated with standard platinum-based chemotherapy with or without bevacizumab, were probed for VEGF-A165b expression by IHC. Results: In patients with low VEGF-A165b expression, the addition of bevacizumab to standard platinum-based chemotherapy significantly improved progression-free (HR: 0.727; 95% CI, 0.538- 0.984; P = 0.039) and overall survival (HR: 0.662; 95% CI, 0.458- 0.958; P = 0.029). Multivariate analysis showed that the addition of bevacizumab in low VEGF-A165b-expressing patients conferred significant improvements in progression-free survival (HR: 0.610; 95% CI, 0.446-0.834; P = 0.002) and overall survival (HR: 0.527; 95% CI, 0.359-0.775; P = 0.001), independently from established risk factors. Conclusions: We demonstrate for the first time that bevacizumab may differentially improve the prognosis of advanced ovarian cancer patients with low expression of VEGF-A165b, an antiangiogenic VEGF-A splice variant. We envision that this novel biomarker could be implemented into routine diagnostics and may have direct clinical implications for guiding bevacizumab-related treatment decisions in advanced ovarian cancer patients.

Original languageEnglish
Pages (from-to)4660-4668
Number of pages9
JournalClinical Cancer Research
Volume28
Issue number21
DOIs
StatePublished - 1 Nov 2022
Externally publishedYes

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