Dual targeting of the epidermal growth factor receptor using the combination of cetuximab and erlotinib: Preclinical evaluation and results of the phase II DUX study in chemotherapy-refractory, advanced colorectal cancer

Abstract

Purpose: This preclinical and phase II study evaluated the efficacy and safety of the combination of cetuximab and erlotinib in metastatic colorectal cancer (mCRC).Patients and Methods: The activity and mechanism of action of the combination of cetuximab plus erlotinib were investigated in vitro in colorectal cancer cell lines. In the clinical study, patients with chemotherapy-refractory mCRC were treated with cetuximab 400 mg/m 2 as a loading dose and then weekly cetuximab 250 mg/m 2 with erlotinib 100 mg orally daily. The primary end point was response rate (RR), which was evaluated separately in KRAS wild-type (WT) versus KRAS mutant tumors. Secondary end points included toxicity, progres..