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

Background: Whether epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) combined with chemotherapy can delay the occurrence of brain metastasis (BM) is unclear.

Objective: This retrospective study aimed to evaluate whether EGFR-TKIs combined with chemotherapy can delay BM and decrease the incidence of BM as initial progression. Patients and

Methods: 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.

Results: The overall median OS was 39 months (95% confidence interval (CI), 35.6-42.4 months). The median OS of EGFR-TKI combined with chemotherapy and EGFR-TKI only are 41 months (95% CI 35.5-46.5 months) and 39 months (95% CI 36.8-41.2 months), respectively. Patients in the combination treatment group had longer PFS (16 vs. 10 months; P = 0.030) and iPFS (21 vs. 14 months; 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 for significant covariables in a multivariable model, the different treatment strategies were independently associated with improved iPFS.

Conclusions: 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.