7568 Background: Erlotinib is now accepted as first line therapy for advanced NSCLC patients with EGFR mutated tumors. However, some patients with EGFR wild-type tumors may benefit as well, and there are no accepted biomarkers to define this subset of patients or to define which patients benefit from chemotherapy. We conducted a single arm phase II trial of erlotinib followed by chemotherapy on progression (carboplatin + paclitaxel +/- bevacizumab) in treatment naïve patients with stage IV NSCLC. Methods: In this multicenter prospective phase II trial, patients with stage IV NSCLC were eligible for enrollment. Blood, frozen tissue and FFPE biopsies for molecular analysis were mandatory at the time of study entry and optional at the time of progression on erlotinib. Additional eligibility included ECOG performance status (PS) 0-2, measurable disease, and adequate marrow, renal and hepatic function. Patients with stable treated brain metastases were allowed. Patients were treated with erlotinib 150 mg daily until disease progression at which time they underwent a biopsy and were switched to carboplatin/paclitaxel +/- bevacizumab. Disease status was assessed after 4 weeks of erlotinib to detect early progression. Results: From 10/07 to 06/11, 127 patients were enrolled: 59% male, 90% Caucasian, 6% African American, 4% Asian, 30% never smokers. 7 patients failed screening. Among evaluable patients on erlotinib, 13% had PR, 48% SD, and 27% PD. Median PFS on erlotinib was 4.7 months (95% CI 3.5 to 8.3 months). In patients who went on to receive chemotherapy on protocol, 24% had PR, 27% SD, and 20% PD. In patients who went on to receive chemotherapy on protocol median progression-free survival (PFS) on chemotherapy was 8.1 months (95% CI 5.5 to 10.9 months). Among the 55 patients who did not receive chemotherapy, 23 had a decline in PS, 14 patients refused, 2 patients enrolled on another protocol, and 6 patients had other therapy. Conclusions: This is the first study to report on PFS in unselected NSCLC patients following first line therapy with erlotinib. Translational studies on this large prospectively collected cohort of tissue samples prior to initiation of erlotinib are ongoing.
Combination of Metformin and Gefitinib as First-Line Therapy for Nondiabetic Advanced NSCLC Patients with EGFR Mutations: A Randomized, Double-Blind Phase II Trial