Potential of different prognostic factors according to PD-L1 expression after concurrent chemoradiotherapy with durvalumab in locally advanced NSCLC

Background Concurrent chemoradiotherapy (CCRT) followed by durvalumab is the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC). However, little is known about the established biomarkers for predicting outcomes after such treatments. Methods Between May 2018 and March 2022, we retrospectively analyzed 87 patients with unresectable LA-NSCLC to identify prognostic biomarkers of different variables in this study. Inflammatory and nutritional indices were also correlated with different 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 (GPS). Moreover, L-type amino acid transporter 1 (LAT1), alanine-serine-cysteine transporter 2 (ASCT2), Ki-67, and vascular endothelial growth factor receptor 2 (VEGFR2) were evaluated using immunohistochemistry. Results The high values for NLR, PLR, SII, PNI, and ALI were 51.7% (n = 45), 12.6% (n = 11), 58.6% (n = 51), 19.5% (n = 17), and 87.3% (n = 76), respectively. Immunohistochemical staining demonstrated that high ASCT2, LAT1, Ki-67, and VEGFR2 levels were 68.9% (n = 60), 47.1% (n = 41), 57.4% (n = 50), and 57.4% (n = 50), respectively. In univariate analysis, histology, SII, and GPS were significant prognostic factors for progression-free survival [hazard ratio (HR) with 95% confidence interval (CI); 0.49 with 0.27-0.85, 0.55 with 0.31-0.96, and 0.48 with 0.27-0.89, respectively], while histology, NLR, SII, and GPS were significant predictors of overall survival (HR with 95% CI; 0.40 with 0.19-0.78, 0.51 with 0.25-0.96, 0.44 with 0.21-0.88, and 0.32 with 0.17-0.62, respectively). Sub-analysis according to programmed death ligand-1 (PD-L1) expression identified VEGFR2 (HR = 0.23) as an independent predictor of prognosis in patients with PD-L1 ≥50% (n = 26), GPS (HR = 0.19) in those with PD-L1 1–49% (n = 20), and histology (HR = 0.28), NLR (HR = 0.14), or SII (HR = 0.32) in patients with PD-L1 <1% (n = 32) following CCRT plus durvalumab. Conclusion GPS, NLR, SII, and VEGFR2 were closely associated with promising prognostic markers after CCRT combined with durvalumab. According to sub-analysis, GPS, VEGFR2, and NLR or SII were identified as the possible predictors, especially in patients with PD-L1 1–49%, PD-L1≥50%, and PD-L1<1%, respectively.