A Comparison Between First-, Second- and Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Non-Small-Cell Lung Cancer and Brain Metastases

Patients with non-small-cell lung cancer (NSCLC), harboring Epidermal Growth Factor Receptor (EGFR) mutations, are more susceptible to brain metastases (BM). Comparisons of the efficacy different-generation EGFR-tyrosine kinase inhibitors (TKI) on BMs from NSCLC currently limited. We identified studies comparing different EGFR-TKIs for through Pubmed literature search and selected those neurological outcome data. By two retrospective analyses, Erlotinib showed longer time-to-progression (30 months vs. 15.8 months, P = 0.024) reduced risk central nervous system (CNS) progression (Hazard Ratio (HR) 0.25; 95% CI, 0.08–0.81; 0.021) compared Gefitinib. In a phase 2b randomized trial, 16% patients had similar Progression Free Survival (PFS) (HR 0.76, CI 0.41–1.44) or Overall (OS) 1.16, 0.61–2.21) Afatinib versus Gefitinib; lower developing subsequent than Gefitinib 0.49; 0.34–0.71; < 0.001) was reported by study. A 3 trial proved that treated Osimertinib PFS 0.47, 0.30–0.74) OS 0.79, 0.61–1.01) Gefitinib, incidence CNS (6% 15%, respectively). Although there is limited evidence, differences in activity may exist between EGFR-TKIs.