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

Abstract Background Afatinib is an approved first-line treatment for epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC). Methods Treatment-naive patients with advanced EGFRm+ NSCLC were randomised to afatinib (40 mg/day) versus cisplatin/pemetrexed (LUX-Lung 3 [LL3]) or cisplatin/gemcitabine (LUX-Lung 6 [LL6]), or versus gefitinib (250 mg/day; LUX-Lung 7 [LL7]). We report subgroup analyses by age, including ≥/< 65 years (pre-planned; LL3/LL6) and additional cut-offs up to ≥ 75 years (exploratory; LL7). Progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were evaluated. Results Among the 134/345 (39%) and 86/364 (24%) patients aged ≥ 65 years in LL3 and LL6, median PFS was improved with afatinib versus chemotherapy (LL3: hazard ratio [HR], 0.64 [95% confidence interval, 0.39-1.03]; LL6: HR, 0.16 [0.07-0.39]). Afatinib significantly improved OS versus chemotherapy in elderly patients with Del19+ NSCLC in LL3 (HR, 0.39 [0.19-0.80]). Among the 40/319 (13%) patients aged ≥ 75 years in LL7, median PFS (HR, 0.69 [0.33-1.44]) favoured 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 demonstrate that afatinib is an effective and tolerable treatment for patients with EGFRm+ NSCLC, independent of age. Clinical trial registration ClinicalTrials.gov: NCT00949650, NCT01121393, NCT01466660