Schuler MTan E.-HO'Byrne KZhang LBoyer MMok THirsh VCHIH-HSIN YANGLee K.HLu SShi YKim S.-WLaskin JKim D.-WArvis C.DKölbeck KMassey DMärten APaz-Ares LPark K.2020-05-262020-05-2620190171-5216https://www.scopus.com/inward/record.uri?eid=2-s2.0-85061727826&doi=10.1007%2fs00432-019-02862-x&partnerID=40&md5=14f283969963afb15181926b8ba11c52https://scholars.lib.ntu.edu.tw/handle/123456789/494890Purpose: In the randomized phase IIb LUX-Lung 7 trial, afatinib significantly improved progression-free survival (PFS) and time-to-treatment failure vs gefitinib in patients with treatment-na?ve epidermal growth factor receptor mutation-positive non-small cell lung cancer. We report post hoc analyses of tolerability-guided dose adjustment for afatinib and summarize the clinical characteristics of patients who continued afatinib/gefitinib beyond initial radiological progression in LUX-Lung 7. Methods: Patients received afatinib 40?mg/day or gefitinib 250?mg/day until investigator-assessed progression or beyond if beneficial. In case of selected treatment-related adverse events (TRAEs), the afatinib dose could be reduced by 10-mg decrements to minimum 20?mg (only dose interruptions were permitted with gefitinib). Results: All randomized patients were treated (afatinib, n = 160; gefitinib, n = 159). Sixty-three patients had afatinib dose reduction (< 40?mg/day; 47 within first 6 months). Dose reduction decreased TRAE incidence/severity (before vs after; all grade/grade 3: 100.0%/63.5% vs 90.5%/23.8%). There was no evidence of significant difference in PFS for patients who received < 40?mg/day vs ? 40?mg/day for the first 6 months [median: 12.8 vs 11.0 months; hazard ratio 1.34 (95% confidence interval 0.90–2.00)]. Twenty-four and 26 patients continued afatinib and gefitinib, respectively, beyond progression in target lesions; median time from nadir of target lesion diameters to initial progression was 6.7 months and 5.6 months. Of these patients, ~ 70% had objective response or non-complete response/non-progressive disease in non-target lesions at initial progression. Conclusions: Protocol-defined dose adjustment of afatinib may allow patients to remain on treatment longer, maximizing clinical benefit even in the presence of radiological progression. ? 2019, The Author(s).Afatinib; Dose adjustment; EGFR; NSCLC; Time-to-treatment failure[SDGs]SDG3afatinib; epidermal growth factor receptor; gefitinib; sodium ion; afatinib; antineoplastic agent; EGFR protein, human; epidermal growth factor receptor; gefitinib; protein kinase inhibitor; acne; adult; Article; cancer growth; cancer incidence; clinical assessment; clinical evaluation; controlled study; diarrhea; disease severity; drug dose escalation; drug dose reduction; drug tolerability; female; gene mutation; human; major clinical study; male; multicenter study; nail disease; non small cell lung cancer; patient-reported outcome; phase 2 clinical trial; phase 3 clinical trial; priority journal; progression free survival; randomized controlled trial; rash; stomatitis; time to treatment; treatment duration; treatment failure; aged; brain tumor; clinical trial; disease exacerbation; dose response; enzymology; genetics; lung tumor; middle aged; mutation; non small cell lung cancer; pathology; secondary; very elderly; Adult; Afatinib; Aged; Aged, 80 and over; Antineoplastic Agents; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Disease Progression; Dose-Response Relationship, Drug; ErbB Receptors; Female; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Protein Kinase Inhibitorsjournal article10.1007/s00432-019-02862-x307838142-s2.0-85061727826