The Committee noted the following ongoing clinical trials related to this guidance.
NCT00063141 is an RCT comparing cetuximab combined with irinotecan with irinotecan alone as second-line treatment in patients with metastatic colorectal cancer.
NCT00079066 is an RCT comparing cetuximab combined with best supportive care with best supportive care alone in patients with metastatic colorectal cancer.
The Committee was aware of other ongoing clinical trials with bevacizumab and cetuximab as part of different treatment regimens.
The TREE-2 trial is a randomised multicentre study comparing 3 regimens of oxaliplatin plus bolus, infusional or oral 5-FU with bevacizumab to evaluate safety and tolerability in the first-line treatment of patients with advanced colorectal cancer.
The NO16966C trial is a randomised phase III study of intermittent oral capecitabine in combination with intravenous oxaliplatin (CAPOX) with or without bevacizumab for the first-line treatment of patients with advanced colorectal cancer.
The CONcePT trial aims to develop an optimised schedule of administration of FOLFOX plus bevacizumab in the first-line treatment of patients with advanced colorectal cancer.
The E3200 trial is a phase III RCT of oxaliplatin, 5-FU and leucovorin with or without bevacizumab, versus bevacizumab alone in patients previously treated for advanced or metastatic colorectal cancer. Preliminary data have been presented. The bevacizumab monotherapy arm was prematurely halted because of lack of efficacy.
The first-line use of cetuximab in combination with standard chemotherapy regimens is being investigated in a number of studies. One example is the COIN study (NCT00182715), which aims to determine whether the addition of cetuximab to continuous oxaliplatin and 5-FU improves overall survival when compared with either continuous oxaliplatin and 5-FU on its own, or intermittent oxaliplatin and fluoropyrimidine chemotherapy. Other examples include NCT00145314 (5-FU/FA + oxaliplatin), NCT00286130 (FOLFIRI, FOLFOX) and NCT00215722 (capecitabine and oxaliplatin).
EXPLORE is an RCT comparing cetuximab combined with FOLFOX with FOLFOX alone as second-line treatment in patients with metastatic colorectal cancer. Recruitment to the trial was halted prematurely when the number of participants reached 102. Preliminary results were presented at the annual conference of the American Society for Clinical Oncology in 2005 for progression-free survival and response rate.
The Committee recommends research to investigate the predictive value of EGFR testing and the correlation of baseline and on-treatment markers with tumour response and survival.
Additionally, the Committee recommends studies to investigate the impact of bevacizumab and cetuximab treatment on health-related quality of life.