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

Kommoss, S; Winterhoff, B; Oberg, A; Konecny, GE; Wang, C; Riska, SM; Fan, JB; ... Pfisterer, J; + view all (2017) Bevacizumab may differentially improve ovarian cancer outcome in patients with proliferative and mesenchymal molecular subtypes. Clinical Cancer Research , 23 (14) pp. 3794-3801. 10.1158/1078-0432.CCR-16-2196. Green open access

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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 non-significant improvement in PFS 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: 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.

Type: Article
Title: Bevacizumab may differentially improve ovarian cancer outcome in patients with proliferative and mesenchymal molecular subtypes
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1158/1078-0432.CCR-16-2196
Publisher version: http://doi.org/10.1158/1078-0432.CCR-16-2196
Language: English
Additional information: Copyright © 2017, American Association for Cancer Research.
Keywords: Ovarian cancer, molecular subtypes, bevacizumab, angiogenesis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > Comprehensive CTU at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/1540737
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