Chemotherapy plus cetuximab in patients with liver-limited or non-liver-limited KRAS wild-type colorectal metastases: A pooled analysis of the CRYSTAL and OPUS studies.

Abstract

3562 Background: In the CRYSTAL and OPUS studies, adding cetuximab (cet) to first-line chemotherapy (CT) improved clinical benefit in patients (pts) with KRAS wild-type (wt) metastatic colorectal cancer. In a pooled analysis of these trials the benefit of treatment according to whether pts had liver-limited disease (LLD) or non-LLD was analyzed. Methods: Cox‘s proportional hazards model for overall survival (OS) and progression-free survival (PFS) or logistic regression model for best overall response and R0 resection were used on individual pt data, stratified by study. Likelihood ratio tests were used to explore interactions. Results: Adding cet to CT significantly improved PFS and overall response rate (ORR) in LLD pts, and OS, PFS and ORR in non-LLD pts and increased R0 resection rates (table). No treatment-by-study interactions were found. Treatment effects did not vary significantly by LLD status (PFS p=0.60, OS p=0.68, ORR p=0.0737, R0 resection p=0.71). However LLD vs non-LLD pts had improved outcome in each treatment arm: PFS, CT hazard ratio, HR=0.74, p=0.0910; CT + cet HR=0.66, p=0.0309; OS, CT HR=0.70, p=0.0091; CT + cet HR=0.74, p=0.0388; ORR, CT odds ratio=1.20, p=0.47, CT + cet odds ratio=2.32, p=0.0015; R0 resection, CT odds ratio=3.15, p=0.0496, CT + cet odds ratio=3.82, p=0.0018. Kaplan Meier survival plots will be shown. Conclusions: The OS benefit from adding cet to CT is more pronounced in non-LLD pts, thus strengthening the value of cet in palliative treatment.LLD status is associated with improved prognosis and may be predictive for response in pts receiving CT + cet, facilitating potentially curative resection. More pts (with R0 resection and longer follow-up) may be needed to confirm an OS benefit from CT + cet in LLD pts. [Table: see text]