P-0252 Braf Mutation, Use of Bevacizumab and Survival of Colorectal Cancer

Abstract

ABSTRACT Introduction First-line treatment of metastatic colorectal cancer (mCRC) involves the use of oxaliplatin-based or irinotecan-based chemotherapy combined with one of three monoclonal antibodies ( MoABs): bevacizumab, cetuximab or panitumumab. Finding of mutations in KRAS, BRAF, PI3K, PTEN in the tumor were shown to predict outcomes in patients treated with certain MoAbs. Mutations in BRAF were shown to be markers of poor prognosis and predictors of non-response to anti-EGFR MoABs treatments (cetuximab, panitumumab) in heavily pretreated mCRC patients. Yet, data are still inconclusive on the effect of BRAF mutations on the response of anti-VEGF MoABs (bevacizumab) and anti-EGFR MoABs (cetuximab, panitumumab) when used as first-line treatment. The current retrospective study evaluated the effect on survival of adding bevacizumab as first line treatment of mCRC, in patients with BRAF and/or KRAS mutated and wild type tumors. Methods The study included 333 colorectal cancer patients from the population-based Molecular Epidemiology of Colorectal Cancer (MECC) study in Northern Israel who were treated for their first metastatic event with irinotecan-based or oxaliplatin-based protocols, with or without bevacizumab. Patients were diagnosed between 1998 and 2010 and were followed up until October 2011, surgical intervention for metastatic disease was excluded. Mutations in BRAF codon 600 and in KRAS codons 12, 13, and 61 were identified by direct sequencing and by SNP assay-by-design. Details on treatment were extracted from the oncological follow-up records of the participating cases or computerized pharmacy records. Vital status, date of appearance of metastases and date of death were available for all participants. Results BRAF mutations were detected in 8.2% of the tumors and KRAS mutations in 41.4% of the cases with metastatic disease. Most of the study participants (91%) have died during the follow-up period. First line chemotherapy comprised of Irinotecan based (82%) and oxaliplatin -based (18%). Bevacizumab was recorded in 41% of the cases. The mutations in BRAF (p=0.06), but not in KRAS (p=0.17), was a poor prognostic factor. The effect of BRAF mutations on overall survival (OS) was time-dependent (p Conclusion Our data supports that the addition of bevacizumab to modern combination chemotherapy protocols, based on irinotecan (limited information on oxaliplatin), have a positive effect on OS of mCRC patients, which was highest in patients with BRAF mutated tumors.