Efficacy and safety of first-line afatinib in older patients with advanced EGFR-mutated non-small cell lung cancer

Background/Aims: This study investigated the efficacy and safety of first-line afatinib treatment in older patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Methods: This retrospective, multicenter, observational cohort study included 103 patients aged >= 75 years who were treated with first-line afatinib for EGFR-mutated NSCLC. The primary outcome was time-on-treatment (TOT). Results: The median TOT of patients was 13.6 months (95% confidence interval 11.0-16.2). Ninety-two patients (89.3%) required dose modification. Dose reduction was significantly more frequent in the 40 mg starting dose group than in the 30 mg group (93.1% vs. 68.8%, p = 0.004). The most common grade 3 or worse adverse events (AEs) were diarrhea (n = 16, 54%), acneiform rash (n = 4, 14.3%), and stomatitis (n = 4, 14.3%). Grade 3 or worse AEs led to dose modification in 23 of 28 patients (82.1%) and permanent discontinuation of therapy in five of 28 patients (17.9%). On disease progression, tissue re-biopsy was performed in 18 of 74 patients (24.3%). Thirty-four patients (45.9%) received subsequent chemotherapy; of these, most patients (n = 21, 61.8%) received pemetrexed monotherapy. Conclusions: This study demonstrated the efficacy of first-line afatinib treatment for EGFR-mutant NSCLC in older patients. However, despite similar safety profiles and frequencies of AEs reported in previous studies, the frequency of dose modifications was higher in this population. A 30 mg starting dose of afatinib and a predefined dose adjustment may be suitable strategies for this population. Post-tyrosine kinase inhibitor management, such as tissue re-biopsy and platinum-based chemotherapy, tended to be underprescribed in this age group.