Abstract
Malignant pleural effusion (MPE) is associated with poor prognosis in patients with advanced lung adenocarcinoma (LUAD), and abnormal activation of epidermal growth factor receptor (EGFR) plays a crucial role in the development of LUAD. This study aimed to investigate the correlation between EGFR mutations and the occurrence of MPE in patients with LUAD and evaluate the effect of EGFR mutations on the prognosis of patients with LUAD with MPE. A case-control study design was adopted that included patients pathologically diagnosed with LUAD. Clinical data were collected, and patients were divided into the MPE group and the non-MPE (N-MPE) group based on the presence of MPE. Propensity score matching (PSM) was used to control for confounding factors. The correlation between EGFR mutations and the occurrence of MPE in LUAD was initially examined. Additionally, various factors affecting the overall survival (OS) of patients with LUAD and MPE were evaluated. A total of 849 patients were included in the study. After 1:2 PSM, there were 180 patients in the MPE group and 360 in the N-MPE group. The EGFR mutation rate was significantly higher in the MPE group compared to the N-MPE group [62.7% vs. 50.2%; odds ratio (OR) =1.668; P=0.006]. This difference was primarily attributed to the T790M mutation (8.3% vs. 1.3%; OR =8.015; P<0.001), but no significant differences observed in other mutation sites between the groups. Further evaluation of factors affecting OS in patients with LUAD and MPE revealed that EGFR mutation was an independent protective factor for OS [hazard ratio (HR) 0.662, 95% CI: 0.456-0.962; P=0.03]. For patients with LUAD, MPE, and EGFR mutations, treatment with third-generation EGFR-tyrosine kinase inhibitors (TKIs) alone (HR 0.466, 95% CI: 0.233-0.930; P=0.03) or sequential first- and third-generation EGFR-TKIs (HR 0.385, 95% CI: 0.219-0.676; P=0.001) was associated with better median OS compared to first-generation EGFR-TKIs alone (first-generation EGFR-TKIs: 35 months, 95% CI: 28.4-41.6; third-generation EGFR-TKIs: 50 months, 95% CI: 37.3-62.7; sequential first- and third-generation EGFR-TKIs: 51 months, 95% CI: 45.6-56.4; P<0.001). This study found there to be a positive correlation between EGFR mutations, particularly the T790M mutation, and MPE in patients with LUAD. EGFR mutation was associated with improved OS in patients with LUAD and MPE. For patients with LUAD, MPE, and EGFR mutations, sequential treatment with first- and third-generation EGFR-TKIs or third-generation EGFR-TKIs alone is recommended, as these regimens provide significant benefit to OS.
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