Total blockade of the epidermal growth factor receptor with the combination of cetuximab and gefitinib: A phase I study for patients with recurrent non-small cell lung cancer (NSCLC)

17045 Background: Cetuximab and gefitinib inhibit the epidermal growth factor receptor (EGFR) through different mechanisms. Preclinical evidence suggests that the combination of cetuximab and Gefitinib is synergistic and has shown antitumor activity in vitro and in xenografts (Matar et al, Clin Cancer Res, 2004). We are conducting a phase I study to determine the doses of the two agents that can be administered in combination. Methods: Patients (pts) with advanced NSCLC were eligible upon progression following 1 or 2 prior chemotherapy regimens. Gefitinib was administered at a dose of 250 mg/day for all cohorts. The dose of cetuximab was escalated in sequential cohorts of patients ( table ) and there will be no dose escalation above the approved doses for both agents (dose level 3). Paraffin-embedded tissue samples of the primary cancer were collected from all patients for analysis of EGFR mutations, gene amplification and protein expression. Results: From March to December 2005, 11 patients have been entered to the 3 planned cohorts. Patient characteristics include: 3 women and 8 men, with a median age of 63 years (range 51–77) and ECOG performance status (PS) of: 0 = 50%, 1 = 50%. A total of 26 treatment cycles were administered to the 11 pts with a median of 2 cycles per pt (range 1–8). Other observed adverse events include grade 1/2 skin rash and diarrhea. Of 8 evaluable patients, 4 had stable disease. No DLT has been experienced so far at the projected recommended phase 2 dose (dose level 3). The results of correlative studies will be presented at the meeting. Conclusions: The novel combination of cetuximab and gefitinib is safe and is associated with promising anti-cancer activity in recurrent NSCLC. [Table: see text] [Table: see text]