Kras mutation status and its relationship to treatment outcomes in metastatic colorectal cancer patients treated with anti-vascular endothelial growth factor bevacizumab

Background : The treatment of advanced colorectal cancer (CRC) has improved significantly over recent decades, with targeted or biologic agents providing additional benefit to standard chemotherapyVEGF is an important regulator of physiologic and pathologic angiogenesis and is overexpressed in a wide range of human malignancies. Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that neutralizes VEGF-A. In many studies, although evaluated different types of molecules no identified biomarkers that predict response to antiangiogenic therapy in the clinic so far.This analysis, therefore, was performed to assess the predictive and prognostic impact of KRAS gene mutation status on PFS, OS, and response rate (RR) in patients receiving anti- VEGF therapy.Patients and Methods : The clinical and pathological characteristics of 236 patients with advanced colorectal cancer were retrospectively analyzed in the records of the file from ten different centers. KRAS mutations were detected by polymerase chain reaction from paraffin embedded tissue blocks. FOLFİRİ regimen applied in combination with bevasizumab and less patient as historical IFL, FOLFOX and XELOX regimen was performed.Results : 156 of the 236 patients included in the study KRAS wild-type, mutant KRAS was 80 patients. The median age of patients with KRAS wild-type and mutant group was 54 (23-80) and 54 (18-76), respectively. There were 60 female (38.5%) and 96 male (61.5%) patients in KRAS wild-type group, 29 female (36,3%) and 51 male (63,8%) patients in the KRAS mutant group. The progression free survival was 11,7 months (%95 CI, 9,6 ? 13,8) in the KRAS wild type, 11,9 months (%95 CI, 9,4 -14,5) in the KRAS mutant groups and there was no statistically significant difference (p =0,758).According to the KRAS mutation status, the overall survival of the patients was 35, 1 months (%95 CI,30,9- 39,3) in the KRAS wild type patients, 30,1 months (%95 CI, 25,1-35,1) in the KRAS mutant groups and there was no statistically difference (p =0,231).Conclusion : Unlike EGFR MAbs, there are no predictive markers to assist in patient selection for anti-VEGF therapy. KRAS gene mutation on the effectiveness of anti-VEGF therapy in metastatic colorectal cancer is controversial. At a practical level, K-ras testing is unnecessary to determine which patients should receive bevacizumab and these data also highlight the complexity of K-ras biology in mCRC. These findings should be confirmed prospectively in larger populations. However, patients evaluated with KRAS mutation tests which can be applied as a routine, reliable and for determining the frequency and type of KRAS mutations.Key Words : Metastatic colorectal cancer, Bevacizumab, Angiogenesis KRAS mutation, prognosis.