Bevacizumab and improvement of progression-free survival (PFS) for patients with the mesenchymal molecular subtype of ovarian cancer.

Gynecologic Cancer
Session Type and Session Title: 
Clinical Science Symposium, Finding the Targets in Gynecologic Cancers
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 5509)
Boris J. N. Winterhoff, Stefan Kommoss, Ann L. Oberg, Chen Wang, Shaun M. Riska, Gottfried E. Konecny, Jian-Bing Fan, Viji Shridhar, Ellen L. Goode, Friedrich Kommoss, Andreas Du Bois, Felix Hilpert, Jeremy Chien, Andrew Christopher Embleton, Mahesh Parmar, Richard S. Kaplan, Timothy Perren, Lynn C. Hartmann, Jacobus Pfisterer, Sean Christopher Dowdy; Division of Gynecologic Surgery, Department of Obstetrics and Gynecology, Mayo Clinic Rochester, Rochester, MN; Uni Tuebingen, Tuebingen, Germany; Mayo Clinic, Department of Biostatistics, Rochester, MN; Mayo Clinic, Rochester, MN; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA; Illumina, Inc., San Diego, CA; Mayo Clinic, Department of Experimental Pathology, Rochester, MN; Mayo Clinic, Department of Epidemiology, Rochester, MN; Institute of Pathology, Referral Centre for Gynecopathology, Mannheim, Germany; Kliniken Essen Mitte, Essen, Germany; Department of Obstetrics and Gynecology, University of Schleswig-Holstein, Kiel, Germany; KUMC, Department of Cancer Biology, Kansas City, KS; MRC, London, United Kingdom; MRC Clinical Trials Unit, London, United Kingdom; MRC Clinical Trials Unit at UCL, London, United Kingdom; St James's Institute of Oncology, St. James's University Hospital, Leeds, United Kingdom; Gynecologic Oncology Center, Kiel, Germany

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Abstract Disclosures


Background: ICON7 demonstrated that the addition of bevacizumab to carboplatin and paclitaxel improves progression free survival (PFS), but not overall survival (OS) in first-line treatment of ovarian cancer. Our aim was to determine if response to bevacizumab was associated with the molecular classification as described by The Cancer Genome Atlas (TCGA) project. Methods: Core biopsies from formalin fixed paraffin embedded (FFPE) tissue blocks were examined to ensure >70% tumor nuclei from 425 of 455 ICON7 patients enrolled in Germany. Quality Illumina Whole-Genome DASL HT global gene expression data was generated to stratify 380 (89%) patients into four TCGA subclassifications. Median PFS with 95% confidence intervals (CI) and log rank tests were used to evaluate treatment effect on PFS in the presence of non-proportional hazards. Results: Molecular classification was as follows: 86 were differentiated (23%), 124 immunoreactive (33%), 73 mesenchymal (19%), and 97 proliferative (25%). The groups were balanced over treatment arms. 267 (70.3%) were of serous histology. Patients with serous carcinomas of mesenchymal subtype obtained the greatest benefit from bevacizumab with an improvement of median PFS of 9.5 months (25.5 [95%CI 21.1, NA] vs. 16 [95%CI 10.5, NA] months, p=0.053). In contrast, the differentiated, immunoreactive and proliferative subtypes demonstrated median PFS improvements of 5.8 (19.4 [18.6, NA] vs. 13.6 [9.7, 32.7], p=0.35), 3.4 (17.9 [15.9, NA] vs. 14.6 [12.4, NA], p=0.38) and 3.2 months (21.5 [19.8, 29] vs. 18.3 [13.8, NA], p=0.76), respectively. Patients with mesenchymal tumors or high risk clinical characteristics (suboptimal stage III, all stage IV) (46% of cohort) demonstrated a 7.3 month improvement in median PFS with bevacizumab (19.8 [18.3, 23.7] vs. 12.5 [10.1, 16.2] months, p<0.01). Conclusions: Assignment to molecular subclassifications based on gene expression signatures was feasible using FFPE tissue. Patients with mesenchymal subtype ovarian cancer may be most likely to obtain sustained benefit from treatment with bevacizumab.