Systemic Chemotherapy with and without Anti-EGFR Antibody in the First-line Treatment of Metastatic Colorectal Cancer

Standard systemic chemotherapy has improved the outcome of patients with advanced colorectal rectal cancer (CRC) [1-3], but the disease is still incurable in the majority of patients. Recently, the development of anti-Epidermal Growth Factor Receptor (EGFR) antibody, cetuximab or panitumumab, have provided a new treatment option [4]. Several metastatic colorectal cancer (mCRC) trials have demonstrated the efficacy of anti-EGFR antibodies, as monotherapy [5,6] or combined with chemotherapy [7,8], after the failure of previous chemotherapy treatment. In the first-line setting, building on promising results from phase I/II trial [9], Several phase III studies examining the activity of cetuximab or panitumumab have provided encouraging results [10,11]. First-line treatment with anti-EGFR antibodies has produced a pronounced shift in the treatment framework for patients with mCRC. The substantial clinical benefits of first-line anti-EGFR antibodies treatment for patients with mCRC in the subsequent trials raise this question about whether first-line treatment with the combination of anti-EGFR antibodies and chemotherapy is more beneficial than systemic chemotherapy alone for the overall population or for the molecularly defined subpopulation. With variable results, we did this pooled-analysis to address those issues at least in part. In some trials [10-12], the definition of molecular characteristic of EFGR wildtype mutant has been documented to enable the selection of patients most likely to benefit from particular treatments. We also undertook a subgroup analysis to investigate whether tumor KRAS mutation status was predictive of a favorable outcome to anti-EFGR antibodies plus systemic chemotherapy.