Clinical outcome analysis of different first‑ and second‑generation EGFR‑tyrosine kinase inhibitors in untreated patients with EGFR‑mutated non‑small cell lung cancer with baseline brain metastasis

Currently, the clinical outcomes of patients with epidermal growth factor receptor (<i>EGFR</i>)-mutated non-small cell lung cancer (NSCLC) with baseline brain metastasis receiving first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) are not clear. The present study aimed to assess the clinical outcomes of patients with EGFR-mutated NSCLC with baseline brain metastasis who received first-line first- and second-generation EGFR-TKIs. In the present study, a retrospective analysis of clinical charts was performed to investigate first- and second-generation EGFR-TKIs in patients with <i>EGFR</i>-mutated NSCLC with baseline brain metastasis. Data from 197 patients with <i>EGFR</i>-mutated NSCLC with baseline brain metastasis who received first-line gefitinib, erlotinib or afatinib between May 2013 and January 2020 were retrieved from the Cancer Center database of Chang Gung Memorial Hospital at Linkou for analysis. The systemic objective response rate and intracranial response rate to first-line EGFR-TKIs were 75.1 and 76.1%, respectively. The median progression-free survival (PFS) with first-line EGFR-TKIs, brain metastasis PFS (BMPFS) and overall survival (OS) of all the included patients were 13.07 [95% confidence interval (CI), 11.43-14.70], 24.63 (95% CI, 20.98-28.28) and 28.13 months (95% CI, 23.53-32.74), respectively. According to multivariate analysis, a greater number of brain metastases (>3) and the presence of leptomeningeal carcinomatosis (LMC) were independent predictors of a shorter PFS. Patients with a greater number of brain metastases or LMC also had markedly shorter BMPFS and OS than those with fewer brain metastases or no LMC. First- and second-generation EGFR-TKIs were effective for treating previously untreated patients with <i>EGFR</i>-mutated NSCLC with baseline brain metastasis. In conclusion, for patients whose unfavorable factors [a greater number of brain metastases (>3) and LMCs] are associated with worse clinical outcomes, upfront osimertinib therapy, alone or in combination with other therapeutic strategies and procedures, should be considered.