First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases
Journal
Journal of Thoracic Oncology
Journal Volume
11
Journal Issue
3
Pages
380-390
Date Issued
2016
Author(s)
Abstract
Introduction: Metastatic spread to the brain is common in patients with non-small cell lung cancer (NSCLC), but these patients are generally excluded from prospective clinical trials. The studies, phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations (LUX-Lung 3) and a randomized, open-label, phase III study of BIBW 2992 versus chemotherapy as first-line treatment for patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR activating mutation (LUX-Lung 6) investigated first-line afatinib versus platinum-based chemotherapy in epidermal growth factor receptor gene (EGFR) mutationpositive patients with NSCLC and included patients with brain metastases; prespecified subgroup analyses are assessed in this article. Methods: For both LUX-Lung 3 and LUX-Lung 6, prespecified subgroup analyses of progression-free survival (PFS), overall survival, and objective response rate were undertaken in patients with asymptomatic brain metastases at baseline (n= 35 and n = 46, respectively). Post hoc analyses of clinical outcomes was undertaken in the combined data set (n = 81). Results: In both studies, there was a trend toward improved PFS with afatinib versus chemotherapy in patients with brain metastases (LUX-Lung 3: 11.1 versus 5.4 months, hazard ratio [HR] = 0.54, p = 0.1378; LUX-Lung 6: 8.2 versus 4.7 months, HR = 0.47, p = 0.1060). The magnitude of PFS improvement with afatinib was similar to that observed in patients without brain metastases. In combined analysis, PFS was significantly improved with afatinib versus with chemotherapy in patients with brain metastases (8.2 versus 5.4 months; HR, 0.50; p = 0.0297). Afatinib significantly improved the objective response rate versus chemotherapy in patients with brain metastases. Safety findings were consistent with previous reports. Conclusions: These findings lend support to the clinical activity of afatinib in EGFR mutation-positive patients with NSCLC and asymptomatic brain metastases. ? 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
Subjects
Afatinib; Brain metastases; Epidermal growth factor receptor; NSCLC
SDGs
Other Subjects
afatinib; cisplatin; epidermal growth factor receptor; gemcitabine; pemetrexed; afatinib; antineoplastic agent; EGFR protein, human; epidermal growth factor receptor; platinum complex; quinazoline derivative; adult; aged; brain metastasis; cancer chemotherapy; Conference Paper; drug dose reduction; drug safety; drug tolerability; female; gene mutation; human; major clinical study; male; multiple cycle treatment; non small cell lung cancer; overall survival; phase 3 clinical trial (topic); priority journal; progression free survival; randomized controlled trial (topic); side effect; treatment response; brain tumor; clinical trial; controlled study; enzymology; genetics; lung tumor; metastasis; middle aged; mutation; non small cell lung cancer; pathology; phase 3 clinical trial; randomized controlled trial; secondary; treatment outcome; very elderly; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Neoplasm Metastasis; Organoplatinum Compounds; Quinazolines; Receptor, Epidermal Growth Factor; Treatment Outcome
Publisher
Lippincott Williams and Wilkins
Type
conference paper