197eP Genomic resistance profiles and clinical outcomes of afatinib after first-line osimertinib failure in EGFR-mutated non-small cell lung cancer

at four experienced sites in Vienna.ALK alterations were confirmed by next-generation sequencing.Demographic, clinical, and treatment-related data, including ALKi generation, treatment lines, duration, dose reductions, and treatment holidays, were analyzed descriptively.Results: Twenty-eight patients were included (median age 54 years; 46,4% female).Most patients presented with advanced disease (89.2% stage IV) and adenocarcinoma histology (92.9%).All patients received ALKi in first-line.Overall, 47 lines of treatment were administered to 28 patients.Of these treatment lines, 59.6% (n=28) ended and 40.4% (n=19) are currently ongoing.Second-generation ALKi were more frequently used in first-line (60.7%), whereas third-generation ALKi predominated in later lines.At data cutoff, treatment was ongoing in 63.2% of patients, receiving third-generation ALKi, compared with 33.3% treated with second-generation agents.Overall, the mean duration of treatment was 632.9 days (range: 40-1771) for second generation ALKis and 259.9 days (range: 34-537) for third generation ALKis.Dose reductions occurred more frequently with second-generation ALKi (62.5% vs. 37.5%).Treatment holidays were documented in approximately 22% of patients. Conclusions:In this real-world cohort, ALKi constituted the backbone of palliative treatment in ALK-positive NSCLC.Treatment patterns evolved toward increased use of third-generation ALKi, which were associated with sustained treatment continuation and manageable toxicity profiles.