Empirical Osimertinib as a Second‐Line Treatment Is a Viable Option Following First‐ and Second‐Generation <scp>TKI</scp> Therapy With Unknown <scp>EGFR</scp> Status in Treated Non‐Small Cell Lung Cancer: A Retrospective Study

BACKGROUND AND PURPOSE: Patients with advanced epidermal growth factor receptor (EGFR)-mutated adenocarcinoma often receive frontline first- and second-generation EGFR tyrosine kinase inhibitor (TKI) treatments in Taiwan. However, upon progression, not all patients undergo rebiopsy for molecular testing. In some cases, tumors are located in difficult-to-access areas, and some rebiopsy specimens are inadequate for pathological and molecular assessment. Our aim is to evaluate the efficacy of the third-generation EGFR TKI, osimertinib, in tumors with unknown T790M mutation status. METHODS: This study retrospectively collected data from patients with EGFR-mutant advanced lung adenocarcinoma who received first-line first- or second-generation EGFR TKI therapy followed by the third-generation EGFR TKI osimertinib without rebiopsy to assess T790M mutation status between January 2015 and December 2024. Efficacy and survival outcomes are presented. RESULTS: A total of 160 patients with EGFR-mutated lung adenocarcinoma at clinical stages IIIB-IVB received first- or second-generation EGFR-TKI frontline therapy. After disease progression, 82 patients were treated with osimertinib as a second-line therapy with unknown T790M mutation status. Among them, 48 patients initially received afatinib as frontline treatment, while 34 patients received erlotinib. The best tumor response rate (RR) was 42.7%, with a median time on treatment (ToT) of 5.6 months (95% CI, 4.0-9.3). Swim-plot visualization highlighted a hierarchical pattern wherein longer first-line duration frequently co-occurred with longer empirical second-line duration. CONCLUSION: Osimertinib treatment is a viable option for patients who progress on frontline first- or second-generation EGFR TKI therapy without rebiopsy and have an unknown T790M mutation status. The RR of 42.7% and median ToT of 5.6 months appear consistent with historical outcomes reported for second-line platinum-based chemotherapy. Osimertinib provides an additional treatment line for patients whose tumors are difficult to access and have an unknown T790M status, making it a valuable treatment option for these patients.