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First-line afatinib vs gefitinib for patients with EGFR mutation-positive NSCLC (LUX-Lung 7): impact of afatinib dose adjustment and analysis of mode of initial progression for patients who continued treatment beyond progression

Cited 6 time in Web of Science Cited 5 time in Scopus
Authors
Schuler, Martin; Tan, Eng-Huat; O'Byrne, Kenneth; Zhang, Li; Boyer, Michael; Mok, Tony; Hirsh, Vera; Yang, James Chih-Hsin; Lee, Ki Hyeong; Lu, Shun; Shi, Yuankai; Kim, Sang-We; Laskin, Janessa; Kim, Dong-Wan; Arvis, Catherine Dubos; Kolbeck, Karl; Massey, Dan; Maerten, Angela; Paz-Ares, Luis; Park, Keunchil
Issue Date
2019-06
Citation
Journal of Cancer Research and Clinical Oncology, Vol.145 No.6, pp.1569-1579
Keywords
AfatinibEGFRNSCLCDose adjustmentTime-to-treatment failure
Abstract
PurposeIn 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-naive 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.MethodsPatients received afatinib 40mg/day or gefitinib 250mg/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 20mg (only dose interruptions were permitted with gefitinib).ResultsAll randomized patients were treated (afatinib, n=160; gefitinib, n=159). Sixty-three patients had afatinib dose reduction (<40mg/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<40mg/day vs40mg/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, similar to 70% had objective response or non-complete response/non-progressive disease in non-target lesions at initial progression.ConclusionsProtocol-defined dose adjustment of afatinib may allow patients to remain on treatment longer, maximizing clinical benefit even in the presence of radiological progression.
ISSN
0171-5216
URI
http://hdl.handle.net/10371/165199
DOI
https://doi.org/10.1007/s00432-019-02862-x
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College of Medicine/School of Medicine (의과대학/대학원)Cancer Research Institute (암연구소)Journal Papers (저널논문_암연구소)
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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