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The Fanconi Anemia BRCA Pathway as a Predictor of Benefit from Bevacizumab in a Large Phase 3 Clinical Trial in Ovarian Cancer

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Technical Report,30 Sep 2013,29 Sep 2015

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University of Washington Seattle United States

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The Gynecologic Oncology Group GOG trial 218 was a randomized phase III trial in primary stage III and IV ovarian carcinoma, which found a statistically significant improvement in progression free survival PFS for combination chemotherapy with extended bevacizumab, an antibody to the VEGF receptor that inhibits angiogenesis. We deeply sequences 65 DNA repair genes in germline andor tumor DNA from GOG218 and another upfront clinical trial GOG262. We found that germline or somatic mutations in the BRCA-Fanconi anemia pathway was significantly associated with improved progression-free and overall survival. Moreover, the presence of inherited mutations was not limited to high grade serous carcinomas but was found in most histological sub-type. Finally, we did not identify an interaction between the presence of a BRCA-Fanconi anemia mutation and benefit from bevacizumab in GOG218.

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