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260 ViRP signature predicts response to treatment with chemotherapy and bevacizumab in ovarian cancer – a translational study of the ICON-7 trial’
  1. Kristina Lindemann1,2,3,
  2. Mads H Haugen4,
  3. Jacobus Pfisterer5,
  4. Gunhild M Mælandsmo4,
  5. Stefan Kommoss6,
  6. Ole Christian Lingjærde7,8,
  7. Florian Heitz9,
  8. Jalid Sehouli10,
  9. Rainer Kimmig11,
  10. Boris Winterhoff12 and
  11. Olav Engebraaten2,13,4
  1. 1Department of Gynaecological Cancer, Oslo University Hospital, Oslo, Norway
  2. 2Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
  3. 3NSGO-CTU, Copenhagen, Denmark
  4. 4Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
  5. 5AGO and Gynecologic Oncology Center, Kiel, Germany
  6. 6AGO Study Group and Department of Gynecology and Obstretics, Diakonie-Klinikum Schwäbisch Hall gGmbH,, Schwäbisch Hall, Germany
  7. 7Department of Informatics, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway
  8. 8Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
  9. 9AGO Study Group and Department of Gynecology and Gynecological Oncology, Kliniken Essen-Mitte, Essen, Germany
  10. 10AGO Study Group and Charité – Universitätsmedizin Berlin, Charité Comprehensive Cancer Center (CCCC), Campus Virchow Klinikum, Berlin, Germany
  11. 11AGO Study Group and Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany
  12. 12Department of Obstetrics and Gynecology and Women’s Health, University of Minnesota, Minneapolis, USA
  13. 13Department of Oncology, Oslo University Hospital, Oslo, Norway


Introduction/Background Antiangiogenic therapy using bevacizumab has proven effective for patients with advanced ovarian cancer. However, there is still an unmet need in ovarian cancer to identify patients who benefit from such treatment. The nine-protein signature score vascular endothelial growth factor inhibition response predictor (ViRP) has been shown predictive for response in patients with HER2-negative breast cancer.

Methodology ICON7 was an international, phase 3, open-label, randomized trial assigning patients with either high-risk early-stage disease or more advanced disease to standard chemotherapy +/- bevacizumab, given concurrently and continued in maintenance therapy. DASL gene expression arrays have been performed on FFPE tissue from patients enrolled in the German contribution to the trial. The mRNA based ViRP score was calculated using quantile normalized and probe averaged mRNA expression values and its association with clinical outcome was studied.

Results mRNA expression was available for 359 patients, of whom 189 patients were treated with bevacizumab. We used the earlier determined cut-off <0.3 as a positive ViRP score. Clinical characteristics were balanced across the groups with positive/negative ViRP score. Patients with a positive ViRP score have statistically significant longer progression-free survival with a median of 26.7 months compared to 19.1 months in patients with negative ViRP score (HR 0.58, 95%CI 0.41–0.84, p=0.003). Furthermore, overall survival was significantly longer in patients with a positive ViRP score with median OS not reached compared to 48.2 months in patients with negative ViRP score (HR 0.63, 95%CI 0.41–0.97, p=0.033). Among patients treated with chemotherapy alone ViRP was significantly associated with PFS (HR 0.67, 95%CI 0.46–0.97, p=0.034), but not OS (HR 0.80, 95%CI 0.52–1.23, p=0.31).

Conclusion The ViRP score is predictive for survival benefit of treatment with chemotherapy with bevacizumab in patients with ovarian cancer. This indicates a tumor agnostic signal which identifies patients deriving the largest benefit from adding bevacizumab.

Disclosures KL: Receipt of grants/research supports: GSK, research funding paid to

Institution; Receipt of honoraria or consultation fees: Advisory board fees: Astra Zeneca, Nycode, GSK, Eisai

FH: Receipt of honoraria or consultation fees: Novocure, PharmaMar, Astra Zeneca, Roche, Tesaro, GSK, Clovis, Amedes, NewOncology, Zailab

RK: Receipt of honoraria or consultation fees: Astra Zeneca, MSD; GSK, Roche, Novocure

JS: Research Funding: Institution: AZ, Clovis Oncology, Merck, Bayer, PharmaMar, Pfizer, Tesaro, MSD Oncology, Roche. Consulting/Ad Bds: AZ, Clovis Oncology, PharmaMar, Merck, Pfizer, Tesaro, MSD Oncology, Lilly, Novocure, J&J, Roche, Ingress Health, Riemser, Sobi, GSK, Novartis; Honoraria: AZ, Eisai, Clovis Oncology, Olympus Medical Systems, J&J, PharmaMar, Pfizer, Teva, Tesaro, MSD Oncology, GSK, Bayer; Travel, Accommodations, Expenses: AZ, Clovis Oncology, PharmaMar, Roche Pharma AG, Tesaro, MSD Oncology, Olympus.

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