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Clinical Trial
. 2017 Jul 15;23(14):3794-3801.
doi: 10.1158/1078-0432.CCR-16-2196. Epub 2017 Feb 3.

Bevacizumab May Differentially Improve Ovarian Cancer Outcome in Patients with Proliferative and Mesenchymal Molecular Subtypes

Stefan Kommoss  1 , Boris Winterhoff  2   3 , Ann L Oberg  4 , Gottfried E Konecny  5 , Chen Wang  4 , Shaun M Riska  4 , Jian-Bing Fan  6   7 , Matthew J Maurer  4 , Craig April  7 , Viji Shridhar  8 , Friedrich Kommoss  9 , Andreas du Bois  10 , Felix Hilpert  11 , Sven Mahner  12 , Klaus Baumann  13 , Willibald Schroeder  14 , Alexander Burges  15 , Ulrich Canzler  16 , Jeremy Chien  17 , Andrew C Embleton  18 , Mahesh Parmar  18 , Richard Kaplan  18 , Timothy Perren  19 , Lynn C Hartmann  20 , Ellen L Goode  4 , Sean C Dowdy  21 , Jacobus Pfisterer  22
Affiliations
Clinical Trial

Bevacizumab May Differentially Improve Ovarian Cancer Outcome in Patients with Proliferative and Mesenchymal Molecular Subtypes

Stefan Kommoss et al. Clin Cancer Res. .

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 = 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 = 0.41]. Bevacizumab conferred modest improvements in PFS for patients with immunoreactive subtype (3.8 months; P = 0.08) or differentiated subtype (3.7 months; P = 0.61). Multivariate analysis demonstrated significant PFS improvement in proliferative subtype patients only [HR, 0.45 (95% CI, 0.27-0.74), P = 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. Clin Cancer Res; 23(14); 3794-801. ©2017 AACR.

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Conflict of interest statement

Conflict of interest:

Stefan Kommoss (SK): Roche - consultancy, honoraria; AstraZeneca - honoraria.

Boris Winterhoff (BW): No conflicts of interest.

Ann L. Oberg (ALO): No conflicts of interest.

Gottfried E. Konecny (GEK): Genentech, Consulting; Amgen, Novartis, Research funding

Chen Wang (CW): No conflicts of interest.

Shaun M. Riska (SMR): No conflicts of interest.

Matthew J. Maurer (MJM): No conflicts of interest.

Jian-Bing Fan (JBF): No conflicts of interest.

Craig April (CA): I am an employee and shareholder of Illumina Inc.

Viji Shridhar (VS): No conflicts of interest.

Friedrich Kommoss (FK): No conflicts of interest.

Andreas du Bois (ADB): Personal fees from Roche, MSD, Astra Zeneca, Pharmamar and Amgen.

Felix Hilpert (FH): No conflicts of interest.

Sven Mahner (SM): Roche: Research support, Advisory Board, Honoraria, Travel Support; AstraZeneca: Research support, Advisory Board, Honoraria, Travel Support; Boehringer Ingelheim: Research support, Advisory Board, Travel Support; GlaxoSmithKline: Research support, Advisory Board, Honoraria, Travel Support

Klaus Baumann (KB): Tesaro – advisory board honoraria.

Willibald Schroeder (WS): No conflicts of interest.

Alexander Burges (AB): No conflicts of interest.

Ulrich Canzler (UC): Roche – honoraria.

Jeremy Chien (JC): No conflicts of interest.

Andrew C. Embleton (ACE): No conflicts of interest.

Mahesh Parmar (MP): No conflicts of interest.

Richard Kaplan (RK): No conflicts of interest.

Timothy Perren (TP): No conflicts of interest.

Lynn C. Hartmann (LCH): No conflicts of interest.

Ellen L. Goode (ELG): No conflicts of interest.

Sean C. Dowdy (SCD): No conflicts of interest.

Jacobus Pfisterer (JP): Speakers honoraria from Roche.

Figures

Figure 1
Figure 1
Kaplan Meier analysis of progression free survival for bevacizumab vs. standard treatment stratified by TCGA subtype.
Figure 2
Figure 2
Kaplan Meier analysis of overall survival for bevacizumab vs. standard treatment in patients, stratified by TCGA subtype.
See this image and copyright information in PMC

References

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