Impact of pleural effusion on mortality and hospitalization in stage IV <i>EGFR</i> -mutated NSCLC treated with osimertinib: A real-world analysis.

Abstract

e20646 Background: Pleural effusion (PE) is common in advanced non–small cell lung cancer (NSCLC) and may reflect aggressive disease biology. However, its prognostic significance among patients with stage IV EGFR-mutated NSCLC treated with osimertinib in real-world settings remains incompletely defined. We evaluated long-term mortality and hospitalization outcomes in propensity-matched cohorts with and without PE. Methods: Using the TriNetX US Collaborative Network, adults with stage IV EGFR-mutated NSCLC treated with osimertinib were identified. Stage IV disease was defined by the presence of distant metastatic ICD-10 codes. Inclusion criteria required confirmed EGFR mutation and osimertinib exposure. Patients with non-malignant causes of pleural effusion, end-stage renal disease, heart failure, or prior exposure to other EGFR tyrosine kinase inhibitors were excluded. Patients were stratified by presence versus absence of PE using diagnostic and procedural codes. Cohorts were matched 1:1 using propensity scores based on age at index, sex, race, and ethnicity. Outcomes included all-cause mortality and hospitalization, assessed at 1-, 3-, and 5-year time points. Risk ratios (RR), odds ratios (OR), and Kaplan–Meier survival analyses were performed. Results: A total of 1,061 patients were included in each cohort after application of inclusion and exclusion criteria and 1:1 propensity score matching. Baseline characteristics were well balanced (mean age ~67 years; ~68% female). Mortality was consistently higher in patients with PE compared with those without PE at 1 year (23.9% vs 13.2%; RR 1.81; OR 2.07; HR 2.01), 3 years (36.6% vs 23.8%; RR 1.54; OR 1.85; HR 1.88), and 5 years (38.8% vs 26.4%; RR 1.47; OR 1.77; HR 1.84), all p &lt;0.001. Hospitalization rates were also significantly higher in the PE cohort at 1 year (31.0% vs 18.9%; RR 1.64; OR 1.92), 3 years (37.3% vs 26.0%; RR 1.44; OR 1.69), and 5 years (38.5% vs 27.7%; RR 1.39; OR 1.63), all p &lt;0.001. Survival curves diverged early and remained separated across all time horizons. Conclusions: In this large real-world analysis of stage IV EGFR-mutated NSCLC treated with osimertinib, the presence of pleural effusion was associated with persistently higher mortality and hospitalization rates at 1, 3, and 5 years. Pleural effusion represents a high-risk clinical phenotype despite targeted therapy and may warrant closer monitoring and intensified supportive and oncologic strategies. Propensity-matched demographics. Characteristic Pleural Effusion (n = 1,061) No Pleural Effusion (n = 1,061) Age at index, mean ± SD (years) 67.2 ± 12.0 67.7 ± 11.2 Female sex, n (%) 722 (68.1) 731 (68.9) Male sex, n (%) 339 (31.9) 330 (31.1) Race, n (%) White 617 (58.1) 622 (58.6) Asian 263 (24.8) 262 (24.7) Black or African American 89 (8.4) 92 (8.7) Ethnicity, n (%) Not Hispanic or Latino 838 (79.0) 839 (79.1) Hispanic or Latino 62 (5.8) 56 (5.3)