8072 Background: Sixty percent of EGFR-mutant NSCLC p respond to erlotinib, but overall survival (OS) is the same for upfront chemotherapy. Priming BIM, a pro-apoptotic signaling BH3-only protein, induced sensitivity to erlotinib in EGFR-mutant cell lines (Costa el at. PLoS Med 2007). BIM was related to response and progression-free survival (PFS) in clinical tumor samples, but OS was not reported (Faber et al. Cancer Disc 2011). Mammalian target of rapamycin (mTOR) negatively regulates apoptosis and could influence response to erlotinib. Methods: We assessed static levels of total BIM, BIM-extra long (BIM-EL – a main isoform of BIM), and mTOR mRNA expression and correlated findings with response and OS in 57 erlotinib- or chemotherapy-treated EGFR-mutant NSCLC p in the EURTAC trial. Results: Median age 65; 70.2% female; 59.6% never-smokers; 91.2% adenocarcinoma. Response rate 88.9% for erlotinib-treated p with high total BIM levels, compared to 22.2% with low/intermediate total BIM levels (P=0.0027). Sensitivity/specificity of total BIM as a predictor of response to erlotinib was highly significant (AUC=0.80; P=0.0056). OS was 35.8 months (m) for p with high and 17.7 m with low/intermediate total BIM (P=0.023). Notably, among p with high total BIM, OS was 35.8 m for p with low/intermediate mTOR levels, compared to 20.3 m with high mTOR levels (P=0.4848). In contrast, mTOR did not affect OS in p with low/intermediate BIM (17.5 m vs 25.1 m; P=0.9498). BIM-EL assessment was only possible in 31 p, due to insufficient tumor sample in the remaining p. However, in this subset, BIM-EL seemed to have greater predictive power than total BIM. Conclusions: Our findings highlight the potential usefulness of BIM mRNA as a predictive biomarker of response in EGFR-mutant NSCLC p. Those with low BIM expression could derive only meager benefit from treatment with EGFR TKIs alone but could benefit from synthetic lethality combinations, including BcL-2 inhibitors. Those with high BIM expression could benefit from erlotinib or similar EGFR TKIs, but analysis of mTOR could further improve outcome by selecting p with high mTOR for combination therapy with EGFR TKIs and mTOR inhibitors.