First-line chemotherapy plus cetuximab in patients grouped according to prognostic risk factors: Analysis of the CRYSTAL and OPUS studies.

Abstract

3591 Background: Analysis of randomized trials has shown that mCRC patients (pts) can be divided into prognostic risk groups according to baseline clinical parameters including ECOG performance status, white blood cell count (WBC), alkaline phosphatase (ALP) and number of metastatic (met) sites (Köhne C, et al. Ann Oncol 2002;13:308-17). The effect of adding cetuximab to first-line chemotherapy (CT) on overall survival (OS) in these groups of KRAS wild-type mCRC pts was investigated in the CRYSTAL and OPUS studies. Methods: Pt risk groups were: low-risk (LRG= ECOG 0/1, 1 met site) intermediate-risk (IRG= ECOG <1, >1 met site, ALP <300 U/L or, ECOG>1, low WBC, 1 met site) and high-risk (HRG= ECOG<1, >1 met site, ALP>300 U/L or ECOG>1, high WBC, or ECOG>1, low WBC and >2 met sites). Exploratory analyses comprised estimates of effects using Cox‘s proportional hazards model for OS on individual pt data and comparison of treatment arms by log-rank test. Results: Data are shown in the table. In the pooled analyses, in both treatment arms OS was longest in LRG pts and shortest in HRG pts. Adding cetuximab to CT led to marked improvements in OS in the HRG (Hazard ratio [HR] 0.765, 95% CI 0.506–1.157, p=0.203) and IRG (HR 0.781, 95% CI 0.622–0.981, p=0.033), while improvements in LRG pts (HR 0.869, 95% CI 0.672–1.124, p=0.287) were observed only after prolonged follow up. Data were similar in the separate CRYSTAL and OPUS studies. Conclusions: The analysis confirms the concept of prognostic risk groups for OS according to baseline clinical parameters in pts with KRAS wt mCRC. Benefit from the addition of cetuximab to first-line CT in terms of OS appears to be more pronounced in the IRG and HRG. [Table: see text]