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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.
Polaczek et al. (Fri,) studied this question.