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

Autor:	Kommoss S; Department of Women's Health, Tuebingen University Hospital, Tuebingen, Germany., Winterhoff B; Division of Gynecologic Surgery, Mayo Clinic, Minnesota.; Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic Oncology, University of Minnesota, Minnesota., Oberg AL; Department of Health Sciences Research, Mayo Clinic, Minnesota., Konecny GE; Division of Medical Oncology, UCLA, California., Wang C; Department of Health Sciences Research, Mayo Clinic, Minnesota., Riska SM; Department of Health Sciences Research, Mayo Clinic, Minnesota., Fan JB; AnchorDx Corporation, Guangzhou, China.; Illumina Inc., San Diego, California., Maurer MJ; Department of Health Sciences Research, Mayo Clinic, Minnesota., April C; Illumina Inc., San Diego, California., Shridhar V; Department of Laboratory Medicine, Mayo Clinic, Minnesota., Kommoss F; Institute of Pathology, Mannheim, Germany., du Bois A; Kliniken Essen Mitte (KEM), Deptartment of Gynecology and GynecologicOncology, Essen, Germany., Hilpert F; Department of Gynecology and Obstetrics, Schleswig-Holstein University, Kiel, Germany., Mahner S; Department of Obstetrics and Gynecology, Ludwig Maximillian University Munich, Germany., Baumann K; Department of Gynecology and Gynecologic Oncology, Philipps University Marburg, Germany., Schroeder W; Gynaecologicum Bremen, Bremen, Germany., Burges A; Klinikum der Universitaet Muenchen, Campus Grosshadern, Klinik und Poliklinik fuer Frauenheilkunde und Geburtshilfe, Munich, Germany., Canzler U; Department of Gynecology and Obstetrics, Technical University Dresden, Dresden, Germany., Chien J; Department of Cancer Biology, University of Kansas Cancer Center, Kansas City, Kansas., Embleton AC; Medical Research Council Clinical Trials Unit at University College London, UK., Parmar M; Medical Research Council Clinical Trials Unit at University College London, UK., Kaplan R; Medical Research Council Clinical Trials Unit at University College London, UK., Perren T; Leeds Institute of Cancer Medicine and Pathology, University of Leeds, UK., Hartmann LC; Division of Medical Oncology, Mayo Clinic, Minnesota., Goode EL; Department of Health Sciences Research, Mayo Clinic, Minnesota., Dowdy SC; Division of Gynecologic Surgery, Mayo Clinic, Minnesota. dowdy.sean@mayo.edu., Pfisterer J; Gynecologic Oncology Center, Kiel, Germany.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2017 Jul 15; Vol. 23 (14), pp. 3794-3801. Date of Electronic Publication: 2017 Feb 03.
DOI:	10.1158/1078-0432.CCR-16-2196
Abstrakt:	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 . (©2017 American Association for Cancer Research.)
Databáze:	MEDLINE
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