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

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42 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

Bibliographical note

Funding Information:
A. du Bois is a consultant/advisory board member for Astra Zeneca, Pfizer, PharmaMar, and Roche. F. Hilpert, S. Mahner, and T. Perren report receiving speakers bureau honoraria from and are consultant/advisory board members for Roche. U. Canzler reports receiving speakers bureau honoraria from Astra Zeneca and Roche. J. Pfisterer reports receiving commercial research grants from Roche. No potential conflicts of interest were disclosed by the other authors. The authors would like to thank all collaborating AGO study centers and their affiliated pathologists without whose support this project would not have been possible. This study was financially supported by Mayo Clinic SPORE in ovarian cancer (P50 CA136393), Mayo Clinic Comprehensive Cancer Center (P30 CA015083), Wallace and Evelyn Simmers Career Development Award, and Department of Defense Ovarian Cancer Academy (W81XWH-10-1-0386). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Publisher Copyright:
©2017 AACR.

PubMed: MeSH publication types

  • Journal Article
  • Clinical Trial, Phase III
  • Multicenter Study

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