A composite biomarker based on early dynamic changes in lactate dehydrogenase and PD-L1 expression enhances outcome prediction for immunochemotherapy in HER2-negative advanced gastric cancer

Introduction: Current biomarkers for immunochemotherapy in HER2-negative advanced gastric cancer (AGC) exhibit inadequate predictive accuracy. Therefore, the development of innovative methodologies is imperative for improving patient selection. Methods: In this retrospective biomarker study, a cohort of 107 patients with HER2-negative AGC undergoing first-line immunochemotherapy was examined. Serum biomarkers were serially assessed at baseline and after two treatment cycles. Univariate and multivariate Cox regression analyses, as well as ROC curve analysis, were employed to identify prognostic serum dynamics. A composite biomarker integrating dynamic changes in lactate dehydrogenase (LDH) and a combined positive score (CPS) was developed and validated. Additionally, exploratory genomic profiling was performed. Results: In this study, dynamic changes in LDH were identified as an independent prognostic factor. An increase in LDH of ≥26% after two treatment cycles was associated with significantly poorer progression-free survival (PFS: 5.33 vs. 8.93 months; HR: 2.585, P< 0.001) and overall survival (OS: 13.13 vs. 19.63 months; HR: 2.689, P< 0.001). Consistent results were observed in landmark analyses at the two-cycle timepoint, with significant differences in PFS-landmark (PFS-landmark: 5.17 vs. 8.40 months; HR: 2.450, P< 0.001) and OS-landmark (OS-landmark: 11.76 vs. 19.20 months; HR: 2.538, P< 0.001). Combining LDH dynamics with baseline CPS overcame the predictive limitations observed in patients with CPS