Real-world study on first-line immunochemotherapy in advanced gastric/gastroesophageal junction cancer (GC/GEJC): Predicting response with peripheral immune landscape.

e16023 Background: Immunocheckpoint inhibitors combined with chemotherapy have become the standard first-line treatment for advanced GC/GEJC. Nevertheless, not all patients benefit from IO treatment. A lack of robust predictive biomarkers hampers identification of patients most likely to benefit from immunochemotherapy. This study aims to explore predictive biomarkers and potential mechanisms of first-line immunochemotherapy for advanced GC/GEJC in real-world settings based on blood protein biopsy. Methods: This single-center prospective study comprised advanced GC/GEJC patients confirmed by pathology or imaging who received PD-1 mab (Sintilimab Q3W) and chemotherapy (SOX/XELOX Q3W) in first line regardless of programmed death ligand-1 status. Blood samples were collected at baseline and every two treatment cycles for Olink Target 96 IO analysis. Results: From May 2023 to September 2024, a total of 31 patients were enrolled, with 18 (58%) patients identified as responders (complete response plus primary response) and 13 (42%) as non-responders (progress disease plus stable disease) to the treatment. By September 23, 2024, the overall ORR was 58.0% (95% CI, 39.1-75.5%), the median PFS was 9.6 months (95% CI, 8.3-NA), and mOS had not yet been reached. Lower baseline IL-15 (p = 0.01) and post-treatment MMP12 (p < 0.01) levels were seen in the responders. Additionally, dynamic monitoring revealed that serum PD-L1 expression levels were significantly higher during disease progression compared to the period of maximum tumor regression (p < 0.05). A decline in MUC-16 and MMP12 expression post-treatment was correlated with a more unfavorable PFS. Furthermore, a 5% decrease in MUC-16 expression by the conclusion of the initial two treatment cycles proved effective in the stratification of patients based on their PFS. Conclusions: Our real world, biomarker outcome analysis shows that immunochemotherapy demonstrates promising efficacy in the first-line treatment of advanced GC/GEJ and suggests that anti-angiogenic therapy may be subsequently added in non-responding patients. Additionally, advanced GC/GEJ with IL 15-high expression before treatment may be less effective and may be treated with anti-angiogenic therapy upon progression. Moreover, monitoring PD-L1 levels in responsive patients is crucial, as increase might signal progression. Clinical trial information: ChiCTR2300078000 .