Epidermal Growth Factor Receptor (EGFR)–Tyrosine Kinase Inhibitors (TKIs) Combined with Chemotherapy Delay Brain Metastasis in Patients with EGFR-Mutant Lung Adenocarcinoma

Abstract

Whether epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) combined with chemotherapy can delay the occurrence of brain metastasis (BM) is unclear. This retrospective study aimed to evaluate whether EGFR-TKIs combined with chemotherapy can delay BM and decrease the incidence of BM as initial progression. The data of 100 patients with EGFR-mutant advanced lung adenocarcinoma were retrospectively reviewed. The patients had no BM at initial diagnosis, and BM occurred during the treatment. Patients received EGFR-TKI only or EGFR-TKI combined with chemotherapy. Intracranial progression-free survival (iPFS), systemic progression-free survival (PFS), and overall survival (OS) were evaluated. The overall median OS was 39months (95% confidence interval (CI), 35.6-42.4months). The median OS of EGFR-TKI combined with chemotherapy and EGFR-TKI only are 41months (95% CI 35.5-46.5months) and 39months (95% CI 36.8-41.2months), respectively. Patients in the combination treatment group had longer PFS (16 vs. 10months; P = 0.030) and iPFS (21 vs. 14months; P = 0.026). Further, as initial progression, fewer patients developed BM in the combined treatment group compared with the EGFR-TKI-only group (30.6% vs. 52.9%, P = 0.002) with a hazard ratio of 0.64 (95% CI 0.43-0.96). After controlling forsignificant covariables in a multivariable model, the different treatment strategies were independently associated with improved iPFS. In this retrospective analysis, EGFR-TKIs combined with chemotherapy could improve PFS. Further, the combined treatment could delay BM occurrence and decrease the incidence of BM as initial progression.