TY - JOUR
T1 - Bevacizumab may differentially improve ovarian cancer outcome in patients with proliferative and mesenchymal molecular subtypes
AU - Kommoss, Stefan
AU - Winterhoff, Boris
AU - Oberg, Ann L.
AU - Konecny, Gottfried E.
AU - Wang, Chen
AU - Riska, Shaun M.
AU - Fan, Jian Bing
AU - Maurer, Matthew J.
AU - April, Craig
AU - Shridhar, Viji
AU - Kommoss, Friedrich
AU - Du Bois, Andreas
AU - Hilpert, Felix
AU - Mahner, Sven
AU - Baumann, Klaus
AU - Schroeder, Willibald
AU - Burges, Alexander
AU - Canzler, Ulrich
AU - Chien, Jeremy
AU - Embleton, Andrew C.
AU - Parmar, Mahesh
AU - Kaplan, Richard
AU - Perren, Timothy
AU - Hartmann, Lynn C.
AU - Goode, Ellen L.
AU - Dowdy, Sean C.
AU - Pfisterer, Jacobus
N1 - Publisher Copyright:
©2017 AACR.
PY - 2017/7/15
Y1 - 2017/7/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-16-2196
DO - 10.1158/1078-0432.CCR-16-2196
M3 - Article
C2 - 28159814
AN - SCOPUS:85024105263
SN - 1078-0432
VL - 23
SP - 3794
EP - 3801
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -