Schuler MPaz-Ares LSequist L.VHirsh VLee K.HWu Y.-LLu SZhou CFeng JEllis S.HSamuelsen C.HTang WMärten AEhrnrooth EPark KCHIH-HSIN YANG2020-05-262020-05-2620190169-5002https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065090540&doi=10.1016%2fj.lungcan.2019.04.006&partnerID=40&md5=5f41f398b6b85f8f5707e0116d781864https://scholars.lib.ntu.edu.tw/handle/123456789/494887Objectives: In patients with advanced epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC), first-line afatinib significantly improved progression-free survival (PFS) and objective response vs. platinum-doublet chemotherapy in the phase III LUX-Lung 3 and LUX-Lung 6 trials, and significantly improved PFS, time to treatment failure and objective response vs. gefitinib in the phase IIb LUX-Lung 7 trial. We report post-hoc analyses of efficacy, safety and patient-reported outcomes (PROs) in afatinib long-term responders (LTRs) in these trials. Methods: Treatment-na?ve patients with stage IIIB/IV EGFRm + NSCLC randomized to afatinib in LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 were included in the analysis. Patients treated with afatinib for ? 3 years were defined as LTRs. Results: In LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7, 24/229 (10%), 23/239 (10%) and 19/160 (12%) afatinib-treated patients were LTRs. Baseline characteristics were similar to the study populations, except for the proportions of women (LUX-Lung 3/LUX-Lung 6 only; 92/78% vs. 64% overall) and Del19-positive patients (63–79% vs. 49–58% overall). Median treatment duration among LTRs was 50, 56 and 42 months, and median PFS was 49.5, 55.5, and 42.2 months in LUX-Lung 3/LUX-Lung 6/LUX-Lung 7, respectively. Median overall survival could not be estimated. Frequency of afatinib dose reduction was consistent with the LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 overall populations. PROs were stable in LTRs, with slight improvements after 3 years of afatinib treatment vs. baseline scores. Conclusions: In the LUX-Lung 3/LUX-Lung 6/LUX-Lung 7 trials, 10–12% of afatinib-treated patients were LTRs. Long-term afatinib treatment was independent of tolerability-guided dose adjustment and had no detrimental impact on safety or PROs. ? 2019Afatinib; EGFR TKI; Long-term responder; NSCLC[SDGs]SDG3afatinib; epidermal growth factor receptor; afatinib; antineoplastic agent; EGFR protein, human; epidermal growth factor receptor; gefitinib; platinum derivative; acne; adult; advanced cancer; aged; Article; cancer staging; cancer survival; controlled study; diarrhea; drug efficacy; drug safety; female; human; major clinical study; male; non small cell lung cancer; overall survival; patient-reported outcome; phase 2 clinical trial; priority journal; progression free survival; randomized controlled trial; rash; stomatitis; survival rate; survival time; treatment outcome; clinical trial; dose calculation; genetics; lung tumor; metastasis; middle aged; mortality; mutation; non small cell lung cancer; phase 3 clinical trial; survival analysis; very elderly; Adult; Afatinib; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Dosage Calculations; ErbB Receptors; Female; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Neoplasm Metastasis; Neoplasm Staging; Platinum Compounds; Survival Analysis; Treatment Outcomejournal article10.1016/j.lungcan.2019.04.006312008142-s2.0-85065090540