Background: While epidermal growth factor receptor (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 adult pts with stage IV EGFRm NSCLC who initiated 1L EGFR-TKI, IO (+ chemo), or chemo alone from 5/2017-12/2018, using data from Flatiron Health. Treatment patterns were characterized with respect to timing of EGFRm test results. Kaplan-Meier analysis was used to assess the median duration of therapy (mDoT) and time to next therapy (mTTNT), 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 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, and year of and time from diagnosis to 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 alone 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 alone, pts on EGFR-TKI had longer mDoT (EGFR-TKI: 8.7 months [mo]; IO: 4.8 mo; chemo alone: 3.0 mo, p<0.01) and mTTNT (EGFR-TKI: 12.3 mo; IO: 6.5 mo; chemo alone: 4.0 mo, p<0.01). After adjustment, pts on EGFR-TKI vs pts on IO or chemo alone had significantly lower risk of discontinuing therapy or death (DoT) and initiating second-line therapy or death (TTNT) (see Table). Conclusions: A substantial number of stage IV EGFRm NSCLC pts initiated IO or chemo alone in 1L and EGFR-TKI was associated with better clinical outcomes than IO or chemo alone, highlighting the importance of adhering to NCCN-recommended therapy for these pts.