Trophoblast surface antigen 2 (TROP2) is strongly expressed in patients with non-small cell lung cancer (NSCLC), and its overexpression is closely associated with a worse prognosis. Recently, a novel TROP2-directed antibody–drug conjugate (ADC) has been developed, and TROP2 has been identified as a therapeutic target for NSCLC. In this study, we investigated whether TROP2 expression can predict the outcome after combined immunotherapy with programmed death-1 (PD-1) blockade plus cytotoxic T-lymphocyte antigen-4 (CTLA4) antibody. The present study included 110 patients with advanced NSCLC who received nivolumab plus ipilimumab (Nivo-Ipi) between 2020 and 2022 at our institution. TROP2 and Ki-67 protein expression were evaluated by immunohistochemistry. Inflammatory and nutritional indices were investigated with several variables, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and Glasgow prognostic score. TROP2 was highly expressed in 46 (41.8%) patients, and its overexpression was significantly associated with poor response to Nivo-Ipi therapy. Univariate analysis of all patients identified performance status, liver metastases, bone metastases, NLR, TROP2, PLR, SII, PNI, and ALI as significant predictors of progression-free survival (PFS) and overall survival (OS) after Nivo-Ipi treatment. Multivariate analysis identified TROP2 overexpression as an independent prognostic predictor for PFS and OS. Specifically, TROP2 overexpression was significantly associated with shorter PFS and OS in the subgroups of PD-L1 < 1% or non-adenocarcinoma histology. TROP2 expression could be a significant predictor for outcome after Nivo-Ipi treatment in patients with advanced NSCLC.
Hashimoto et al. (2025) studied this question.