Potential markers predicting bevacizumab efficacy for metastatic colorectal cancer patients.

Abstract

e14107 Background: Fluoropyrimidine-based chemotherapy plus bevacizumab (BV) is standard first-line treatment for metastatic colorectal cancer (mCRC). However, useful markers predicting BV efficacy have not been cleared. The aim of this study was to investigate potential markers of efficacy of BV combined with FOLFOX in mCRC retrospectively. Methods: Eighty-five consecutive patients with previously untreated mCRC were included in this study. All patients received FOLFOX4 plus BV 5mg/kg until progression or unmanageable toxicity occurred. Biomarkers including testing the KRAS gene by DNA direct sequencing as well as clinical factors were evaluated as predictors of outcome. Hazard ratios (HR) and 95% confidence intervals (CI) for survival were estimated using the Cox proportional hazards analysis. Results: The overall response and disease control rate was 61.2% and 95.3% respectively. The median progression-free survival (PFS) and time to treatment failure (TTF) were 18.4 and 13.1 months respectively. Two-year survival rate was 65.9%. In univariate analysis, small number of metastatic site (N-meta), good tumor response (TR), temporary interruption of oxaliplatin (L-OHP) and continuance of BV as clinical factors and normal CA125, ALP and LDH levels as biomarkers were associated with better PFS and overall survival (OS). Normal D-dimer level significantly prolonged PFS and TTF. KRAS gene status (72.7% wild-type, 27.3% mutant) did not impact on TR, PFS, TTF or OS. According to multivariate analysis results, TR (HR 0.24; 95%CI 0.12-0.48, p < 0.001) and normal LDH level (HR 0.13; 95%CI 0.06-0.29, p < 0.001) were associated with better PFS. TR (HR 0.11; 95%CI 0.03-0.43, p = 0.002), N-meta (HR 0.38; 95%CI 0.12-0.74, p = 0.004) and dose reduction of 20% for L-OHP (HR 0.07; 95%CI 0.02-0.29, p < 0.001) were significantly associated with better OS. Conclusions: This study suggests that continuing L-OHP and BV accepting appropriate interruption due to adverse events were considered to improve survival for mCRC patients receiving L-OHP-based chemotherapy plus BV. Moreover, CA125, ALP, LDH and D-dimer may have the possibility to be predictive biomarkers of outcome, but KRAS gene status could not be a predictor. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chugai Pharma, Yakult Honsha Co.