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
Journal
Journal of Cancer Research and Clinical Oncology
Journal Volume
145
Journal Issue
6
Pages
1569-1579
Date Issued
2019
Author(s)
Schuler M
Tan E.-H
O'Byrne K
Zhang L
Boyer M
Mok T
Hirsh V
Lee K.H
Lu S
Shi Y
Kim S.-W
Laskin J
Kim D.-W
Arvis C.D
Kölbeck K
Massey D
Märten A
Paz-Ares L
Park K.
Abstract
Purpose: 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).
Subjects
Afatinib; Dose adjustment; EGFR; NSCLC; Time-to-treatment failure
SDGs
Other Subjects
afatinib; 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 Inhibitors
Publisher
Springer Verlag
Type
journal article