Pharmacokinetic and pharmacogenomic analysis of low-dose afatinib treatment in elderly patients with EGFR mutation-positive non–small cell lung cancer

An increasing number of advanced non–small cell lung cancer (NSCLC) cases are being reported in the ageing population. However, studies on the use of afatinib in elderly patients are scarce. We conducted a prospective multicentre, single-arm, and open-label phase II trial for low-dose afatinib (30 mg/day) use in elderly patients with NSCLC with EGFR mutation to assess quality-of-life (QOL) and pharmacokinetic (PK)/pharmacogenomic (PGx) parameters. The primary end-point was the objective response rate (ORR), and the planned number of registered cases was 35, with a threshold ORR of 50%, an expected ORR of 75%, α of 0.05, and β of 0.1. Secondary end-points were progression-free survival (PFS), overall survival (OS), the incidence rate of adverse events (AEs), QOL survey (FACT-L), and trough plasma concentration of afatinib at steady state (Css) and at the occurrence of clinically significant AEs. The median age of the patients was 79 years. The ORR was 80.0% and the disease control rate was 91.4%. The median PFS and OS were 15.6 and 29.5 months, respectively. Four patients discontinued because of AEs. Treatment-related death was not observed. No significant change in QOL was observed at baseline and after 4, 8, and 12 weeks. Css was comparable with those in previous reports and was significantly higher in patients with grade 3 AEs. Direct correlations between afatinib treatment and PGx profiles were not observed. An afatinib starting dose of 30 mg/day could be an effective and safe treatment option for elderly patients. •Objective response rate was 80.0% and disease control rate was 91.4%.•Progression-free and overall survival were 15.6 and 29.5 months, respectively.•Plasma level of 30 mg afatinib was comparable with that of LUX-LUNG studies.•Plasma afatinib level in patients with grade 3 adverse events was relatively high.•Afatinib starting dose of 30 mg/day may be effective for elderly patients.