The role of maintenance therapy in the first line treatment of metastatic colorectal cancer

Abstract

Introduction: mFOLFOX6þantiEGFR antibody is a standard-of-care in the 1st line chemotherapy of metastatic colorectal cancer. Two molecular targeted drugs, i.e. cetuximab (Cet) and panitumumab (Pani), are the choices of antiEGFR antibody, but the proper use of these drugs are not clarified yet. Cet, IgG subclass1 antibody, is demonstrated to have ADCC activity and other immune, inflammatory functions. Differences of the activities of these two antibodies could be analyzed from this standpoint using the kinetic evaluations of neutrophil-to-lymphocyte ratio (NLR), which is the indicator of cancer-related immune and inflammatory activities. Methods: 50 pts with RAS wild metastatic colorectal cancer were enrolled and treated with mFOLFOX6þantiEGFR antibody (25 pts with Cet, 25 pts with Pani). NLR was measured at the points of pre-treatment (preT), early-tumor-shrinkage (ETS) and gression of disease (PD). The associations of NLR and clinical outcomes were evalua ing by Spearman's rank correlation coefficient, and two-sample Mann-Whitney U were performed with several variants between Cet and Pani pts. Results: The median follow-up time for censored cases was 28 months (m) (IQR, 14-52). Progression free survival (PFS) and overall survival (OS) were 10.9m (95% C.I;7.9-12.6) and 30.0m (95% CI; 20.4-41.2), respectively. PFS and OS of Cet and Pani pts were not different significantly different [PFS: 12.0m (95% CI; 7.2-16.2) vs 9.5m (95% CI; 7.8-12.1), p ¼ 0.23; OS: 30.0m (95% CI; 21-49.9) vs 33.1m (95% CI; 13-41.9), p ¼ 0.202]. NLR at preT and PD were significantly correlated with OS, -0.291(p ¼ 0.0422) and -0.347 (p ¼ 0.0413), respectively. Correlation of PFS with NLR at ETS and with the difference of NLR between preT and ETS, were -0.415 (p ¼ 0.0391) and -0.355 (p ¼ 0.0816) in Cet pts, whereas there were no significant trends of correlation in Pani pts, 0.272 (p ¼ 0.209) and 0.598 (p ¼ 0.002), respectively. Conclusion: Our results suggest that NLR kinetics could reflect the treatment outcomes and kinetic analysis would lead to the stratification of clinical use of Cet and Pani. Cet, rather than Pani, might have more immune and inflammatory associations in the 1st line chemotherapy of RAS wild metastatic colorectal cancer. Clinical trial information: UMIN000031535.