Background: Although it has been suggested that results of EGFR-IHC, EGFR-FISH and EGFR and KRAS mutations are predictive of EGFR-TKIs efficacy, they are not used in clinical practice. ERMETIC is a French NCI granted prospective study aiming to facilitate implementation of these biomarkers in France. Methods: After a preliminary phase of validation in 16 French centers, these biomarkers were studied in available tumor specimens collected from all consecutive NSCLC patients (pts) treated by erlotinib, for the first time. Patients were followed-up until progression or death. Demographic, clinical, pathological characteristics and biomarkers were studied by Cox model as predictors of progression free survival (PFS) and overall survival (OS). Results: 493 of the 530 enrolled pts between 02/07 and 03/08 are included in this analysis, among whom at least 357 (72%) tumor specimens were collected. 88% were Caucasians, 32% females; median age was 62 (33-93); 15% were never smoker, 67% former and 15% active. 18% were PS0, 51% PS1 and 31% PS2-3. 92% pts were metastatic and 66% had adenocarcinoma (ADC). Erlotinib (150 mg in 98% of pts) was given as first-, second- and third-or-more-line in 10, 45, 42% of pts, respectively. 94% of pts had received previous platin-based chemotherapy. With a 11.5 months (mo.) median of follow-up, PFS was 2.4 mo. and OS 5.6 mo., with a 30% 1-year OS. Clinical factors independently associated with shorter OS were: PS1 and PS2-3 (HR=1.79 and 4.3, p<.0001); histology other than ADC and squamous cell (HR=1.44 and 1.03, p=.05); 2 sites of metastasis and more (HR=1.60 and 1.82, p<.0001) and former and active smoking (HR=1.49 and 2.12, p=.002). In multivariate analysis, line of treatment was not prognostic. Conclusions: The study confirmed in a large cohort of advanced NSCLC treated by erlotinib the independent value of several prognostic factors. Prognostic values of EGFR-IHC, EGFR-FISH and EGFR and KRAS mutations will be reported at the meeting.