CEA response and depth of response (DpR) to predict clinical outcomes in patients (pts) with metastatic colorectal cancer (mCRC) treated with first-line cetuximab plus oxaliplatin-based chemotherapy: A sub-analysis of the JACCRO CC-05/06 trials.

Abstract

648 Background: Carcinoembryonic antigen (CEA) decrease was faster and greater in cetuximab (cet) treatment than bevacizumab treatment and correlated with prolonged survival in mCRC pts receiving FOLFIRI plus cet (Michl M, et al. Ann Oncol 2016). We investigated if the CEA decrease is a surrogate for DpR reported to be associated with clinical outcomes. Methods: This study evaluated the association between the percentage of CEA decrease or DpR and clinical outcomes in pts with KRAS exon 2 wild-type from 2 phase II trials of 1st-line therapy; JACCRO CC-05 of cet plus FOLFOX ( n= 57, UMIN000004197) and CC-06 of cet plus SOX ( n= 61, UMIN000007022). The association was analyzed using Spearman’s rank correlation coefficient. The cut-off value of 75% CEA decrease was used for CEA response to discriminate CEA responders according to the previous report. The DpR was defined as the percentage of tumor shrinkage at the nadir as compared with the baseline values. Results: In total of 113 pts of the 2 trials in the full analysis set, 92 were eligible for analyses of both CEA and DpR. In the population consists of 92 evaluable pts, median progression-free survival (PFS) was 9.1 months, and median overall survival (OS) was 36.2 months. Median CEA decrease was 67.4% and median time to CEA nadir was 2.8 months similar to median time to DpR of 3.0 months. The DpR was associated with PFS and OS (rs= 0.56; P< 0.0001, rs= 0.39; P= 0.0090, respectively); moreover, CEA decrease correlated with PFS (rs= 0.56, P< 0.0001) as well as OS (rs= 0.35, P= 0.019). CEA responders showed significantly longer PFS [11.8 vs. 5.5 months; hazard ratio (HR) 0.46; 95% Cl, 0.28–0.73; P= 0.0009] and numerically longer OS (36.2 vs. 23.5 months; HR 0.57; 95% CI, 0.30-1.05; P= 0.072) than CEA non-responders. The CEA decrease was statistically significantly associated with DpR (rs= 0.44, P< 0.0001). Conclusions: Our study demonstrates that DpR and CEA response both correlated with clinical outcomes of 1st-line treatment with cet plus oxaliplatin-based chemotherapy. The CEA decrease may serve as a surrogate for DpR in 1st-line cet treatment.