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

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 (EGFRmthorn) non-small-cell lung cancer (NSCLC). Patients and Methods: Treatment-naive patients with advanced EGFRmthorn 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. (C) 2018 The Authors. Published by Elsevier Inc.