Bevacizumab may differentially improve ovarian cancer outcome in patients with proliferative and mesenchymal molecular subtypes

Stefan Kommoss, Boris Winterhoff, Ann L. Oberg, Gottfried E. Konecny, Chen Wang, Shaun M. Riska, Jian Bing Fan, Matthew J. Maurer, Craig April, Viji Shridhar, Friedrich Kommoss, Andreas Du Bois, Felix Hilpert, Sven Mahner, Klaus Baumann, Willibald Schroeder, Alexander Burges, Ulrich Canzler, Jeremy Chien, Andrew C. EmbletonMahesh Parmar, Richard Kaplan, Timothy Perren, Lynn C. Hartmann, Ellen L. Goode, Sean C. Dowdy, Jacobus Pfisterer

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Purpose: Recent progress in understanding the molecular biology of epithelial ovarian cancer has not yet translated into individualized treatment for these women or improvements in their disease outcome. Gene expression has been utilized to identify distinct molecular subtypes, but there have been no reports investigating whether or not molecular subtyping is predictive of response to bevacizumab in ovarian cancer. Experimental Design: DASL gene expression arrays were performed on FFPE tissue from patients enrolled on the ICON7 trial. Patients were stratified into four TCGA molecular subtypes. Associations between molecular subtype and the efficacy of randomly assigned therapy with bevacizumab were assessed. Results: Molecular subtypes were assigned as follows: 122 immunoreactive (34%), 96 proliferative (27%), 73 differentiated (20%), and 68 mesenchymal (19%). In univariate analysis patients with tumors of proliferative subtype obtained the greatest benefit from bevacizumab with a median PFS improvement of 10.1 months [HR, 0.55 (95% CI, 0.34–0.90), P ¼ 0.016]. For the mesenchymal subtype, bevacizumab conferred a nonsignificant improvement in PFS of 8.2 months [HR 0.78 (95% CI, 0.44–1.40), P ¼ 0.41]. Bevacizumab conferred modest improvements in PFS for patients with immunoreactive subtype (3.8 months; P ¼ 0.08) or differentiated subtype (3.7 months; P ¼ 0.61). Multivariate analysis demonstrated significant PFS improvement in proliferative subtype patients only [HR, 0.45 (95% CI, 0.27–0.74), P ¼ 0.0015]. Conclusions: Ovarian carcinoma molecular subtypes with the poorest survival (proliferative and mesenchymal) derive a comparably greater benefit from treatment that includes bevacizumab. Validation of our findings in an independent cohort could enable the use of bevacizumab for those patients most likely to benefit, thereby reducing side effects and healthcare cost.

Original languageEnglish (US)
Pages (from-to)3794-3801
Number of pages8
JournalClinical Cancer Research
Volume23
Issue number14
DOIs
StatePublished - Jul 15 2017
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Bevacizumab may differentially improve ovarian cancer outcome in patients with proliferative and mesenchymal molecular subtypes'. Together they form a unique fingerprint.

  • Cite this

    Kommoss, S., Winterhoff, B., Oberg, A. L., Konecny, G. E., Wang, C., Riska, S. M., Fan, J. B., Maurer, M. J., April, C., Shridhar, V., Kommoss, F., Du Bois, A., Hilpert, F., Mahner, S., Baumann, K., Schroeder, W., Burges, A., Canzler, U., Chien, J., ... Pfisterer, J. (2017). Bevacizumab may differentially improve ovarian cancer outcome in patients with proliferative and mesenchymal molecular subtypes. Clinical Cancer Research, 23(14), 3794-3801. https://doi.org/10.1158/1078-0432.CCR-16-2196