Background: While EGFR tyrosine kinase inhibitors (TKIs) are the NCCN-recommended first-line (1L) therapy for non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutation (EGFRm), many pts initiate immunotherapy (IO) + chemotherapy (chemo) prior to receiving EGFRm test results. This study assessed clinical outcomes associated with initiating EGFR-TKI vs other therapies in stage IV EGFRm NSCLC. Methods: A retrospective study was conducted in adults with stage IV EGFRm NSCLC who initiated 1L EGFR-TKI, IO (+ chemo), or chemo alone from 5/2017-12/2018, using Flatiron Health Electronic Health Record data. Treatment patterns were characterized with respect to timing of EGFRm test results. Kaplan-Meier analysis and log-rank tests were used to evaluate the median duration of therapy (DoT) and time to next therapy (TTNT), as proxies for progression-free survival. Adjusted hazards ratios (HR) and 95% confidence intervals (CI) representing the effect of 1L therapy on the risk of discontinuing treatment or death (DoT) and the risk of initiating second-line therapy or death (TTNT) were reported from multivariable Cox proportional hazards models controlling for differences in demographics, smoking history, histology, cancer stage, ECOG score, NCI index, time from diagnosis to 1L initiation, and year of 1L initiation, across treatment arms. Results: Among 593 study pts, mean age was 67.5 years and 65.4% were female. EGFR-TKI was used as 1L therapy for 77.2% of pts (n=458), IO in 13.3% (n=79) and chemo in 9.4% (n=56). 7.2% of EGFR-TKI pts, 54.4% of IO pts, and 57.1% of chemo pts initiated 1L before receiving EGFRm test results. Compared to pts on IO and chemo, pts on EGFR-TKI had longer median DoT (EGFR-TKI: 8.7 months [mo]; IO: 4.8 mo; chemo: 3.0 mo, p<0.01) and median TTNT (EGFR-TKI: 12.3 mo; IO: 6.5 mo; chemo: 4.0 mo, p<0.01). Adjusted analyses showed that compared to pts on IO or chemo, pts on EGFR-TKI had significantly lower risk of discontinuing therapy or death (DoT) and initiating second-line therapy or death (TTNT) (Table). Conclusions: Substantial numbers of pts initiated IO + chemo in 1L and EGFR-TKI was associated with better clinical outcomes than IO + chemo, suggesting the importance of adhering to NCCN-recommended therapy for stage IV EGFRm NSCLC pts.