2531 Background: A direct correlation between anti–epidermal growth factor (EGF)antibody titers and survival was demonstrated in vaccinated patients with novel NSCLC advanced in Phase II studies. We show the results of treatment with anti-EGF vaccine in a cohort of patients with metastatic NSCLC after progressing to first line therapy. We evaluated immunogenicity, safety, treatment response and effect on survival. Methods: 12 patients with metastatic NSCLC after progressing to first-line therapy received anti EGF-vaccine alone or in combination with chemotherapy. Results: From October 2009 until August 2011, 12 patients started treatment with anti EGF vaccine; mean age 56.5 (42-79 y); 66.7% male; ECOG 0 and 1: 41.7% and 58,3% respectively. Adenocarcinoma (50%), bronchioloalveolar (33.3%), adenosquamous (16.7%). Metastatic sites: lung (41.7%), pleura (25%), CNS (16.7%), Kidney (8.3%). In addition to chemotherapy previous used: radiotherapy (50%), surgery (41.7%), erlotinib (41.7%), bevacizumab (25%). The 50% patients received vaccine alone. The 83.3% of patients had titers 1/4000 sera dilutions or more (good responders). According to RECIST 1.1: CR: 8.3%, PR: 16.7%, SD: 41.7%, PD 25%. Median overall survival was 18.8 months (95% CI: 13.3- 24.4 m). Median progression-free survival was 7.3 months (95% CI: 6.4 -8.2 m). We found no statistically significant differences in OS and PFS when comparing vaccine alone or combined (p = 0.181 and p = 0.801). 75% of patients had adverse effect: more frequently were: 42.4% application site pain, 15.1% fever and 10.38% chills, none of them serious. Conclusions: Vaccination anti EGF in patients with metastatic NSCLC after progressing to first line, alone or in combination, was safe and provoked an increase in anti-EGF antibody titers, produced clinical benefit, improved overall survival and progression free survival.