Background: Osi is a 1L therapy for EGFR mutant lung cancer based on the results of the FLAURA clinical trial. Patients on clinical trial are typically highly selected and the overall effectiveness of therapies may be lower in the real-world setting. We report the real-world outcomes of patients treated with first line osi and compare the outcomes of trial eligible and ineligible patients. Methods: Pharmacy records from January 2020 to October 2022 were used to retrospectively identify patients who received 1L osi for advanced EGFR mutant (exon 19 del. or exon 21 L858R) lung cancer in British Columbia, Canada. Patients were deemed ineligible for the FLAURA trial if they met one of five criteria: ECOG ³2, unstable brain metastases (symptomatic or on steroids), hemoglobin <90, platelet <100, or creatinine clearance <50. Comparisons of overall survival (OS) and time to treatment discontinuation (TTD) were made between using Kaplan-Meier survival curves and log-rank testing. Hazard ratios (HR) are reported using Cox regression adjusting for baseline factors (Table). Results: Of 312 patients included, 133 (43%) were considered FLAURA-ineligible. Reasons for ineligibility were poor ECOG (n=120 [including ECOG 2=69, ECOG 3=48, and ECOG 4=4]), unstable brain metastases (n=21), anemia (n=7), thrombocytopenia (n=5), and low creatinine clearance (n=9). Median follow up was 22.7 months. At the time of analysis, 103/133 (77%) of ineligible patients had discontinued osi and 87/133 (65%) had died. 82/179 (45%) of eligible patients had discontinued osi and 53/179 (30%) were deceased. The median TTD in the ineligible group was 11.9 months (95% CI 10.5-15.5) vs 26.9 months (95% CI 21.9- 34.6) in the eligible group (p<0.001), HR 2.1 (95% CI 1.5-2.9, p<0.001). The median OS in the ineligible group was 15.8 months (95% CI 12.4 to 21.1) vs NR [not reached] (95%CI 28.5 to NR) in the eligible group (p<0.001), HR 2.6 (95% CI 1.8-3.7, p<0.001). Rates of dose reduction for toxicity were similar between ineligible (25%) and eligible (19%) patients (p=0.25). Second-line therapy was received by 28/102 (27%) of trial ineligible patients and 46/82 (56%) of trial eligible patients. Conclusions: Over 40% of the real-world population receiving 1L osi would have been ineligible for the FLAURA clinical trial. These patients had significantly inferior outcomes. This study provides benchmark data to better inform patient prognosis using real-world data.