In the CRYSTAL and OPUS studies, adding cetuximab to first-line chemotherapy (CT) improved clinical benefit in patients with KRAS wild-type (wt) metastatic colorectal cancer. In a pooled analysis of these trials, the benefit of treatment according to whether patients 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 patient data, stratified by study. Likelihood ratio tests were used to explore interactions.Results
Adding cetuximab to CT significantly improved PFS (median 11.9 versus 9.2 months, hazard ratio [HR] 0.53, P = 0.0095) and overall response rate (ORR, 72.0 versus 43.2%, odds ratio 3.51, P < 0.0001) in LLD patients, and OS (median 22.0 versus 17.3 months, HR 0.76, P = 0.0023), PFS (median 9.4 versus 7.4 months, HR 0.68, P = 0.0004) and ORR (52.8 versus 37.2%, odds ratio 1.88, P < 0.0001) in non-LLD patients. An increase in R0 resection rates for both patients with LLD (11.8 versus 5.3%, odds ratio 2.38, P = 0.1121) and non-LLD (3.3 versus 1.7%, odds ratio 1.97, P = 0.1870) was also observed. No treatment-by-study interactions were found. Treatment effects did not vary significantly by the LLD status (PFS: P = 0.60, OS P = 0.68; ORR: P = 0.0737; R0 resection: P = 0.71). However, LLD versus non-LLD patients had improved outcomes in each treatment arm: PFS, CT HR 0.74, P = 0.0910; CT + cetuximab HR 0.66, P = 0.0309; OS, CT HR 0.70, P = 0.0091; CT + cetuximab HR 0.74, P = 0.0388; ORR, CT odds ratio 1.20, P = 0.47, CT + cetuximab odds ratio 2.32, P = 0.0015; R0 resection, CT odds ratio 3.15, P = 0.0496, CT + cetuximab odds ratio 3.82, P = 0.0018.Conclusions
The OS benefit from adding cetuximab to CT is more pronounced in non-LLD patients, thus strengthening the value of cetuximab in palliative treatment. The LLD status is associated with improved prognosis and may be predictive for response in patients receiving CT + cetuximab, facilitating potentially curative resection. More patients (with R0 resection and longer follow-up) may be needed to confirm an OS benefit from CT + cetuximab in LLD patients.