Identification of poor prognostic factors using circulating extracellular vesicles in durvalumab consolidation therapy for locally advanced non-small cell lung cancer.

Background: The risk factors associated with treatment resistance to consolidation durvalumab following chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC) have not been well established.

Methods: Extracellular vesicles (EVs) were isolated from the pretreatment serum of 73 patients treated with consolidation durvalumab. Isolation was performed using CD9/CD63 antibodies, and EV proteins were identified using liquid chromatography-tandem mass spectrometry (LC-MS). The relationship between the expression of these proteins and progression-free survival (PFS) after durvalumab initiation was analyzed.

Results: The median PFS was not reached(NR) (95 % confidence interval [CI], 17.2 months-NR), andthe 24-month PFS rate was 54.7 % (95 % CI, 44.4-67.4). Proteomic analysis of circulating EVs identified RPS27A, SAA1, and S100A7 as the primary candidate biomarkers. Notably, patients with high RPS27A expression exhibited a significantly shorter PFS compared with those with low expression; hazard ratio (HR) 2.93 (95 % CI: 1.48-5.79),P = 0.002. Similarly, high SAA1 expression was associated with a shorter PFS; HR 2.94 (95 % CI: 1.37-6.30), P = 0.006. High S100A7 expression also correlated with poorer outcomes; HR 2.94 (95 % CI: 1.43-6.04), P = 0.003. In multivariate analysis, a high expression level of RPS27A was identified as an independent predictor of poor PFS; HR 2.29 (95 % CI: 1.01-5.17), P = 0.047. Multivariate receiver operating characteristic (ROC) analysis incorporating these three proteins yielded an area under the curve (AUC) of 0.71 (95 % CI: 0.59-0.83).

Conclusion: This study demonstratedfavorable PFS outcomes in patients receiving durvalumab consolidation therapy. Circulating EV proteomic analysis identified RPS27A, SAA1, and S100A7, particularly RPS27A, as potential biomarkers for predicting resistance to durvalumab.