BackgroundIt’s widely accepted that Obesity is closely associated with the elevated risk of various cancers. However, there’s no consensus regarding the impact of body mass index (BMI) on the outcome of targeted therapy targeted-therapy efficacy in lung cancer. MethodsTreatment-naive advanced NSCLC patients harboring EGFR mutation prescribed TKI were screened and enrolled from 3 referral centers. Patients enrolled from West China Hospital were set as the training group, and the others as validation group. Both the demographic features including mutation status and BMI, and therapeutic effects including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were collected.ResultsIn the training group, patients were dichotomized according to their BMI. Those with higher BMI (>22.5) achieved a prolonged PFS compared with those with lower BMI (13.8 and 10.9 mon, HR: 0.68; 95% CI: 0.54-0.86; P = 0.001), and the priority persisted irrespective of different cut-off values. Besides, the favorable association of high BMI with long PFS was confirmed in the validation cohort (14.0 and 11.6 mon, P=0.089) and whole cohort (13.7 and 11.3 mon, P=0.004). In the multivariate analysis, BMI was an independent favorable factor of PFS, together with gender, albumin, and performance. By integration of these factors, a nomogram to predict to 1-,3-year PFS was established. Finally, higher BMI was associated with better objective response rate (ORR, 74% and 69%) and longer overall survival (OS, 41.4 and 33.5 mon, P=0.011). ConclusionHigh BMI was independently associated with efficacy of EGFR-TKI treatment in advanced NSCLC patients.