Afatinib as First-line Treatment of Older Patients With EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Subgroup Analyses of the LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7 Trials
Journal
Clinical Lung Cancer
Journal Volume
19
Journal Issue
4
Pages
e465-e479
Date Issued
2018
Author(s)
Wu Y.-L
Sequist L.V
Tan E.-H
Geater S.L
Orlov S
Zhang L
Lee K.H
Tsai C.-M
Kato T
Barrios C.H
Schuler M
Hirsh V
Yamamoto N
O'Byrne K
Boyer M
Mok T
Peil B
Märten A
Paz-Ares L
Park K.
Abstract
There are limited data on the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in older patients. In these subanalyses of the LUX-Lung 3, 6, and 7 trials, the efficacy of first-line afatinib in older patients with EGFR mutation-positive non-small-cell lung cancer was consistent with the overall study populations, with no unexpected safety signals. Progression-free survival was improved versus platinum-doublet chemotherapy (LUX-Lung 3/6) or gefitinib (LUX-Lung 7). Background: Afatinib is approved in the US, Europe, and several other regions for first-line treatment for epidermal growth factor receptor mutation-positive (EGFRm + ) non-small-cell lung cancer (NSCLC). Patients and Methods: Treatment-naive patients with advanced EGFRm + NSCLC were randomized to afatinib (40 mg/d) versus cisplatin/pemetrexed (LUX-Lung 3 [LL3]) or cisplatin/gemcitabine (LUX-Lung 6 [LL6]), or versus gefitinib (250 mg/d; LUX-Lung 7 [LL7]). We report subgroup analyses according to age, including 65 years or older versus younger than 65 years (preplanned; LL3/LL6) and additional cutoffs up to 75 years and older (exploratory; LL7). Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. Results: Among the 134 of 345 (39%) and 86 of 364 (24%) patients aged 65 years and older in LL3 and LL6, median PFS was improved with afatinib versus chemotherapy (LL3: hazard ratio [HR], 0.64 [95% confidence interval (CI), 0.39-1.03]; LL6: HR, 0.16 [95% CI, 0.07-0.39]). Afatinib significantly improved OS versus chemotherapy in elderly patients with Del19 + NSCLC in LL3 (HR, 0.39 [95% CI, 0.19-0.80]). Among the 40 of 319 patients (13%) aged 75 years or older in LL7, median PFS (HR, 0.69 [95% CI, 0.33-1.44]) favored afatinib, consistent with the overall population. Afatinib-associated AEs in older patients were consistent with the overall populations. Conclusions: Subgroup analyses of the LL3, LL6, and LL7 trials show that afatinib is an effective and tolerable treatment for patients with EGFRm + NSCLC, independent of age. ? 2018 The Authors
Subjects
EGFR blocker; Elderly; Gefitinib; NSCLC; Tyrosine kinase inhibitor
SDGs
Other Subjects
afatinib; alanine aminotransferase; aspartate aminotransferase; cisplatin; epidermal growth factor receptor; gefitinib; gemcitabine; pemetrexed; afatinib; antineoplastic agent; cisplatin; deoxycytidine; EGFR protein, human; epidermal growth factor receptor; gefitinib; gemcitabine; pemetrexed; acne; age; aged; alanine aminotransferase level; anemia; Article; aspartate aminotransferase level; cancer chemotherapy; cancer patient; carcinogenesis; conjunctivitis; decreased appetite; diarrhea; drug dose reduction; drug efficacy; drug tolerability; drug withdrawal; dry skin; fatigue; female; gene mutation; human; interstitial lung disease; leukocyte count; leukopenia; major clinical study; male; multiple cycle treatment; nausea; neutropenia; neutrophil count; non small cell lung cancer; overall survival; paronychia; phase 2 clinical trial (topic); phase 3 clinical trial (topic); post treatment survival; progression free survival; pruritus; rash; side effect; stomatitis; treatment duration; vomiting; adult; analogs and derivatives; clinical trial; controlled study; genetics; lung tumor; middle aged; mortality; mutation; non small cell lung cancer; phase 2 clinical trial; phase 3 clinical trial; randomized controlled trial; Adult; Afatinib; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cisplatin; Deoxycytidine; ErbB Receptors; Female; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Pemetrexed; Progression-Free Survival
Publisher
Elsevier Inc.
Type
journal article