Comparing the effects of afatinib with gefitinib or Erlotinib in patients with advanced-stage lung adenocarcinoma harboring non-classical epidermal growth factor receptor mutations

Objective: Approximately 10%-15% patients with epidermal growth factor receptor (EGFR) mutations harbor non-classical mutations. However, the effects of EGFR-tyrosine kinases (TKIs), particularly second-generation EGFR-TKI (afatinib) compared to first-generation EGFR-TKIs (gefitinib/erlotinib), in patients with non-classical EGFR mutations remain unknown. Methods: We conducted this retrospective study at the China Medical University Hospital (Taichung, Taiwan) from June 2011 to July 2016. Specimens from 1632 patients were tested for EGFR mutations. We surveyed the effectiveness of afatinib and gefitinib/erlotinib in stage IIIb-IV lung adenocarcinoma patients with non-classical EGFR mutations. Results: Fifty-six patients with advanced-stage (stage IIIB-IV) lung adenocarcinoma with non-classical mutations and receiving EGFR-TKI treatment had completed follow-up and were further analyzed. Afatinib versus gefitinib/erlotinib showed that the objective response rates were 62.5% versus 50.0% (p = 0.35). Median progression-free survival (PFS) of 11.0 versus 3.6 months (p = 0.03), respectively, was observed for the 51 non-classical EGFR mutated (excluding 5 patients with exon 20 insertions) lung adenocarcinomas. Subset analysis showed that PFS curves of afatinib were more easily distinguished in non-classical EGFR mutations lacking a combination with a classical mutation (non-classical with classical complex mutations group: median PFS, 11.0 versus 8.2 months, p = 0.19; non-classical mutation alone or in combination with other non-classical mutations group: median PFS, 18.3 versus 2.8 months, p = 0.07). Conclusions: Afatinib may be a first-choice EGFR-TKI for patients with advanced-stage lung adenocarcinomas harboring non-classical mutations.