Background: Among mNSCLC patients positive for EGFR mutation (EGFRm), first-line (1L) treatment with an EGFR TKI is recommended for best outcomes. This study describes real-world treatment patterns of mNSCLC patients using EGFR TKIs in the 1L setting, including osimertinib, the most recently approved EGFR TKI for 1L use. Methods: Patients with ≥1 claim for an EGFR TKI (1st generation [1G]: gefitinib, erlotinib; 2nd generation [2G]: afatinib, dacomitinib; 3rd generation: osimertinib) from January 1, 2015 – April 30, 2020 were identified in IQVIA’s prescription (LRx) and medical claims (Dx) databases; first date of EGFR TKI was the index date. Patients had 12-month baseline period before index, variable follow-up after index, ≥1 lung cancer diagnosis on index or in baseline, and earliest metastatic cancer diagnosis on or 90 days before index. Kaplan-Meier analysis was used to estimate 1L treatment duration, where treatment discontinuation was defined as >60-day gap in medication supply of the index EGFR TKI. Patient characteristics and treatment patterns were stratified by 1L EGFR TKI. Results: Overall, 2,505 mNSCLC patients received 1L EGFR TKI (982 osimertinib, 1,060 1G, 463 2G). Median ages were 66-69 years, 64.6-67.1% were female, and 32.4-38.9% had central nervous system metastases on or before index. Most patients were commercially insured (50.8-62.9%), 35.3-45.9% had Medicare, and 0.6-3.3% had other payer types. Nearly all patients had 1L EGFR TKI monotherapy (97.6-99.7%). 1L treatment duration was longer for osimertinib compared to 1G or 2G EGFR TKI (median months, 17.8, 8.7, 10.5 respectively). 2L treatment was observed in 32.5% of 1G and 36.3% of 2G EGFR TKI cohorts. Osimertinib monotherapy, chemotherapy, and immunotherapy (monotherapy or combined with chemotherapy) accounted for 58.3%, 7.0%, and 4.3% of 2L treatments after 1L 1G EGFR TKI, respectively, and 60.7%, 4.2%, and 4.8% of 2L treatments after 1L 2G EGFR TKI. Conclusions: In real-world practice, 1L treatment duration is longer with osimertinib compared with other EGFR TKIs. Future studies with longer follow-up are recommended to understand treatment patterns after progression on EGFR TKIs, mainly osimertinib, given its recent approval.