For pts with metastatic NSCLC and a sensitizing EGFR mutation, osi is standard treatment, either in first line (1L) or beyond (2L+, if T790M+). Limited osi efficacy data is available in relation to plasma trough levels, as well as elderly or those with low or high BMI. Retrospective Dutch multicentre (two academic, one non-academic) study. Eligible: pts ≥18 years, with metastatic EGFR+ NSCLC regularly treated with osi. Start date of osi was used as index date, data was extracted from medical files. Primary endpoint: progression free survival (PFS). Secondary endpoint: overall survival (OS), objective response rate (ORR, RECIST v1.1) and disease control rate (DCR). Kaplan-Meier and multivariate Cox proportional hazard models were used to compare different subgroups for age, BMI and steady state plasma trough levels (Cmin,SS), measured <3 months (m) before disease progression (age [<70 / ≥70], BMI [<18.5 / 18.5 – 24.9 / 25.0 – 29.9 / >30] and plasma trough level [<149 / 149 – 259 / >259]). In total 294 pts were included: mean age 67 years (range = 29 – 87 years), mean BMI 25.3 (range = 17.6 – 67.1), 35% male, 90% Caucasian, 54% exon 19 deletion, 30% L858R, 17% other. Osi was given in 1L (n = 118, 40%), 2L (n = 134, 46%) or beyond (3L+, n=42, 14%). Median PFS was 14.6 m (95% CI = 10.2 – 20.0) (1L), 13.7 m (95% CI = 11.1 – 15.6) (2L) and 8.7 m (95% CI = 5.1 – 12.7) (3L+). ORR and DCR were similar in all lines (1L: 68% and 96%, 2L: 62% and 93% and 3L+: 69% and 91%). Pts ≥70 years at osi start achieved similar PFS and OS compared to pts <70 years (PFS: aHR = 0.93; 0.68 – 1.28; OS: aHR = 1.14; 0.77 – 1.68). Low BMI (<18.5) led to lower absolute effectiveness (PFS and OS), but not statistically significant, due to the low number of pts in the subgroup (n = 8). A high plasma trough concentration was associated with lower PFS (aHR = 1.92, 95% CI = 1.10 – 3.37). PFS and OS with 1L osi were lower compared to those found in the FLAURA trial, while in 2L survival was slightly longer in daily practice. Age was not associated with PFS, while a low BMI and a high Cmin,SS may be correlated with worse treatment outcomes on osi.