Real world data and biomarker analysis of the efficacy and safety of PD-1 inhibitor combined with chemotherapy in first-line treatment of advanced gastric cancer.
Authors: Xiaoting Ma, Kai Ou, Wenwei Yang, Biyang Cao, Lin Yang
Journal: Journal of Clinical Oncology (2025)

342 Background: With the publication of several clinical research results, the efficacy of ICI combined with chemotherapy has gradually been recognized in HER-2 negative advanced GC field. We analyzed the efficacy of 1st-line PD-1 inhibitor combined with chemotherapy in advanced GC patients using real-world data and conducted exploratory analysis. We aim to identify factors that can predict treatment efficacy, and provide a basis for clinical practice. Methods: We prospectively collected data from GC patients between November 2020 and April 2024. The clinical staging was stage IV. All patients were HER2 negative and pMMR. All patients received SOX regimen chemotherapy combined with PD-1 inhibitor. Blood samples were collected for exploratory analysis. Results: A total of 190 GC patients with histological diagnosis of adenocarcinoma were included from November 1, 2020 to April 1, 2024. As of June 1, 2024, the median follow-up time was 11.75 (95% CI 10.65-13.00) months. Among them, 174 had measurable lesions. 94 patients achieved PR, and 55 patients achieved SD. The ORR and DCR were 61.9% (95% CI 48.8-73.4%) and 96.8% (95% CI 89.0-99.6%), respectively. The survival analysis results indicated that the mPFS and mOS were 9 (95% CI 7.9-14.2) and 27 (95% CI 20- not reached) months. We conducted risk factor analysis on patients , age, gender, CPS, HER2 expression, EGFR expression and EBER status. Age, gender, CPS, EBER status and EGFR expression are not risk factors affecting survival. Specifically, the expression level of HER2 was significantly correlated with therapeutic efficacy. The results indicated that the HER2 expression level was significantly correlated with ORR. In terms of survival analysis, the PFS of treated patients with HER2 ‘2+’ was significantly longer than that of treated patients with HER2 ‘1+’, and there was a trend of prolonged OS, but the statistical difference was not reached. We collected baseline blood samples from 62 patients and performed ctDNA testing. In terms of PFS, the patients with SNV in SMARCA4 and RASA1 was significantly shorter than that of wild-type patients with SMARCA4 ( p = 0.02) and RASA1 ( p = 0.043). The patients with CNV in EXT1 was significantly shorter than those with wild-type in EXT1 ( p = 0.00046). In terms of OS, patients with SNV in BRCA2, TP53, and STK11 had significantly shorter OS than those with wild-type BRCA2 ( p = 0.033), TP53 ( p = 0.048), and STK11 ( p = 0.0083). The patients with CNV in MYC and EXT1 had shorter OS than those with wild-type MYC ( p &lt; 0.0001) and EXT1 ( p &lt; 0.0001) patients. Conclusions: Real-world data showed that 1st-line treatment with PD-1 inhibitor combined with SOX had shown good efficacy in advanced GC patients. The HER2 expression level in HER2 negative GC may become a direction for further exploration. The EXT1 mutation can serve as a potential predictor, and further investigation is warranted. Clinical trial information: NCT06034964 .