TROP2 expression as a prognostic predictor for osimertinib in patients with EGFR-mutant non-small cell lung cancer

Osimertinib is the standard first-line treatment for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC); however, clinical outcomes vary widely even among patients receiving uniform therapy. Reliable baseline prognostic biomarkers beyond EGFR mutation subtype remain limited. Trophoblast cell-surface antigen 2 (TROP2) has been implicated in tumor progression and therapeutic resistance, but its prognostic relevance in EGFR-mutated NSCLC treated with first-line osimertinib remains unclear. Therefore, this study aimed to evaluate the prognostic significance of TROP2 expression in patients with EGFR-mutated NSCLC treated with first-line osimertinib.

We retrospectively analyzed 155 patients with recurrent or metastatic EGFR-mutated NSCLC who received first-line osimertinib monotherapy between August 2018 and December 2023. TROP2 expression was evaluated by immunohistochemistry using a semi-quantitative scoring system calculated as the product of staining intensity (0-3) and proportion score (1-4), yielding a total score ranging from 0 to 12. TROP2 overexpression was defined as a total score of 12. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method and Cox proportional hazards models.

TROP2 overexpression was observed in 72 patients (46.5%). While TROP2 overexpression was not independently associated with PFS, it was associated with shorter OS in the overall cohort. In multivariate analysis, age, performance status, clinical stage, liver metastasis, and TROP2 overexpression were identified as independent prognostic factors for OS. Subgroup analysis showed that TROP2 overexpression was associated with worse OS in patients with EGFR exon 19 deletion, whereas this association was not evident in those with L858R mutation. TROP2 intensity score showed stronger prognostic relevance than the proportion score.

TROP2 overexpression is an independent predictor of poor OS in patients with EGFR-mutated NSCLC receiving first-line osimertinib. These findings suggest that baseline TROP2 expression may reflect biologically aggressive disease and support further exploration of TROP2-targeted strategies after EGFR-TKI resistance.