Garassino M.C.He Y.Ahn M.J.Orlov S.V.Potter V.Kato T.Laskin J.Voon P.J.Reungwetwattana T.Ramalingam S.S.Wu Y.L.Albayaty M.Cross S.L.Huang X.Kulkarni D.Cho B.C.Mahidol University2025-03-192025-03-192025-04-01Lung Cancer Vol.202 (2025)01695002https://repository.li.mahidol.ac.th/handle/20.500.14594/106722Introduction: This post-hoc analysis of the registrational FLAURA study and AURA program reports long-term safety data in epidermal growth factor receptor-mutated (EGFRm), advanced non–small cell lung cancer (NSCLC) treated with osimertinib for ≥ 36 months. Methods: Patients from FLAURA who received first-line osimertinib and from the AURA program (AURA, AURA2, AURA3) who received ≥ second-line osimertinib were included. Patients received osimertinib 80 mg once daily. Safety data were analyzed in patients who remained on treatment for ≥ 36 months. The post-study global safety database captured investigator-reported serious adverse events (SAEs) in patients who continued osimertinib beyond final data cut-off (DCO) of the studies. Best response data were analyzed in patients on treatment for ≥ 54 months (FLAURA) or ≥ 36 months (AURA program). Results: In FLAURA, 76 (28 %) and 36 (13 %) of 267 patients received first-line osimertinib for ≥ 36 and ≥ 54 months, respectively; median exposure: 52.5 and 64.5 months, respectively. Across the AURA program,124 (16 %) of 799 patients received ≥ second-line osimertinib for ≥ 36 months; median exposure: 44.7 months. Investigators reported on-study SAEs in 17 % (FLAURA) and 35 % (AURA program) of patients who continued treatment for ≥ 36 months. Post-study incidences of SAEs were 11 % (FLAURA) and 21 % (AURA program). On-study, adverse events (AEs) of cardiac effects (indicative of cardiac failure; grouped term) occurred in 7 % (FLAURA) and 5 % (AURA program) of patients; AEs of interstitial lung disease (ILD; grouped term) occurred in 0 (FLAURA) and 1 (AURA program) patient. No post-study SAEs were reported for the grouped terms cardiac effects and ILD. Most patients treated for ≥ 54 months (FLAURA) and ≥ 36 months (AURA program) had a best on-study response of partial response. Conclusion: This analysis demonstrated that long-term treatment with osimertinib of ≥ 36 months was well tolerated in patients with EGFRm advanced NSCLC.Biochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1016/j.lungcan.2025.1084172-s2.0-8600013367518728332