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469 Angiogenesis gene variants as biomarkers for bevacizumab-induced toxicities: a translational subproject of the prospective randomized phase III trial AGO-OVAR 17
  1. Rahel Polaczek1,
  2. Florian Heitz2,
  3. Dhanya Ramachandran1,
  4. Peter Hillemanns1,
  5. Jörn Rau3,
  6. Philipp Harter2,
  7. Martin L Heubner4,
  8. Ulrich Canzler5,
  9. Christian Jackisch6,
  10. Klaus Baumann7,
  11. Barbara Schmalfeldt8,
  12. Alexander Burges9,
  13. Lars Ch Hanker10,
  14. Andreas D Hartkopf11,
  15. Tjoung-Won Park-Simon12,
  16. Antje Belau13,
  17. Dominik Denschlag14,
  18. Willibald Schröder15,
  19. Thilo Dörk1 and
  20. Jacobus Pfisterer16
  1. 1Hannover Medical School, Hannover, Germany, Hannover, Germany
  2. 2AGO Study Group and Evangelische Kliniken Essen-Mitte, Essen, Germany, Essen, Germany
  3. 3AGO Study Group and Coordinating Center for Clinical Trials, Philipps-University Marburg, Marburg, Germany, Marburg, Germany
  4. 4AGO Study Group and University Hospital Essen, Essen, Germany and Cantonal Hospital Baden AG, Baden, Switzerland, Essen, Germany
  5. 5AGO Study Group and University Hospital Carl Gustav Carus, Technische Universität Dresden and National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany
  6. 6AGO Study Group and Sana Hospital Offenbach, Offenbach, Germany
  7. 7AGO Study Group and University Hospital Gießen and Marburg, Site Marburg, Marburg, Germany and Hospital Ludwigshafen, Ludwigshafen, Germany;, Ludwigshafen, Germany
  8. 8AGO Study Group and Hospital Rechts der Isar, Technical University Munich, Munich, Germany and University Medical Center Hamburg-Eppendorf, Hamburg, Germany;, Hamburg, Germany
  9. 9AGO Study Group and University Hospital LMU Munich, Department of Obstetrics and Gynecology, Munich, Germany, München, Germany
  10. 10AGO Study Group and University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
  11. 11AGO Study Group and University Hospital Tübingen, Tübingen, Germany
  12. 12AGO Study Group and Hannover Medical School, Hannover, Germany
  13. 13AGO Study Group and University Hospital Greifswald, Greifswald, Germany and Frauenarztpraxis Dr. Belau, Greifswald, Germany
  14. 14AGO Study Group and Hochtaunus-Kliniken, Hospital Bad Homburg, Bad Homburg, Germany
  15. 15AGO Study Group and GYNAEKOLOGICUM Bremen, Bremen, Germany, Bad Homburg, Germany
  16. 16AGO Study Group and Gynecologic Oncology Center, Kiel, Germany


Introduction/Background Bevacizumab is a monoclonal antibody against soluble VEGF, active in the treatment of various cancer entities and one standard in the primary treatment of patients with advanced ovarian cancer. Toxicity profile of bevacizumab is favorable, however, hypertension and renal toxicites are specific side effects, which might lead to therapy discontinuation. No predictive biomarkers are available to identify patients with high risks of these toxicities.

Methodology AGO-OVAR17 was a multicenter, open-label, randomized phase III trial including 927 ovarian cancer patients proofing that a treatment duration with bevacizumab of 15 months was equal effective to 30 months. German patients treated within the trial (N=764) could be included to our subproject, if they were still in the trial. After informed consent, genomic DNA was extracted from peripheral blood and subjected to SNPtype array genotyping of 24 polymorphisms known or suspected to regulate VEGF levels or VEGF activity. Genotypes were associated with clinical toxicity variables using linear or logistic regression analyses in STATA.

Results During the recruitment period of 16 months, 131 patients were included. Genotyping was successful in all patients. 22 of the 24 variants passed QC and showed call rates > 99%. Association analyses with clinical variables revealed a potential association of rs58159269 and rs1885657, two linked variants in VEGFA, with residual disease. Delayed occurrence of toxicity events was observed for three carriers of the rare allele of rs114694170, a variant upstream of MEF2C (p=0.03).

Conclusion We found borderline associations of VEGFA variants with residual disease and of a rare variant rs114694170 with toxicity after bevacizumab. Larger studies will be needed to replicate these initial results.

Disclosures Nothing to disclose.

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