Efficacy and safety of serplulimab-based therapy in HER2-negative advanced gastric cancer: A real-world study.

e16031 Background: Serplulimab is an anti-PD-1 inhibitor demonstrating promising anti-tumor activity and is recommended for the treatment of microsatellite instability-high or deficient mismatch repair (MSI-H/dMMR) gastric cancer. In this real-world cohort study, we aimed to explore the efficacy and safety of serplulimab-based treatment in HER2-negative advanced gastric cancer patients. Methods: Adult patients with histologically or cytologically confirmed HER2-negative advanced gastric cancer who received serplulimab-based therapy at the First Affiliated Hospital of Soochow University were eligible for this real-world study. The primary endpoint was objective response rate (ORR), and the secondary endpoints included disease control rate (DCR), real-world progression-free survival (rwPFS), overall survival (OS), duration of response (DoR), and adverse events (AEs). Results: Between April 2022 and October 2024, 49 patients (49/71, 69.0%) received first-line serplulimab-based therapy, and 22 (22/71, 31.0%) treated in the later lines were included in this analysis. The median age was 65 years (range 35-80), 71.8% (n = 51) were males, and 60.6% (n = 43) had an ECOG score of 0. The majority received a combination of chemotherapy (n = 56, 78.9%), with taxanes+platinum-based (n = 30, 42.3%) regimen being the most common, followed by fluorouracil+taxanes-based (n = 15, 21.1%), fluorouracil+platinum-based (n = 8, 11.3%), and fluorouracil+taxanes+platinum-based (n = 3, 4.2%) regimen. The ORR and DCR were 47.2% (95% CI: 33.3-61.4) and 90.6% (95% CI: 79.3-96.9), respectively. As of December 23, 2024, the median follow-up duration was 8.4 months. The median rwPFS of all patients was 10.6 months (95% CI: 7.2-NR), 15.9 months (95% CI: 8.0-NR) for patients who received taxanes+platinum-based regimen, and 23.7 months (95% CI: 23.7-NR) for patients treated with fluorouracil+taxanes-based regimen. Subgroup analysis revealed that the median rwPFS in patients receiving a first-line serplulimab-based regimen (14.9 months; 95% CI: 8.4-NR) was statistically significantly longer than those treated in the later lines (4.0 months; 95% CI: 2.3-NR), with a hazard ratio (HR) of 0.39 (95% CI: 0.19-0.81; P = 0.011). Median OS was not reached; the first-line serplulimab treatment showed a superior 1-year OS rate than in later lines (93.8% vs. 49.6%), and patients treated with the fluorouracil+taxanes-based therapy achieved a higher 1-year OS rate than taxanes+platinum-based regimen (100.0% vs. 81.3%). The median DoR was 8.5 months (95% CI: 4.3-NR). A total of 30 patients (42.3%) reported any grade AEs; 12 (16.9%) experienced grade 3-4 AEs, and myelosuppression (n = 6, 10.9%) was the most common. Conclusions: Our real-world study demonstrated that serplulimab-based therapy has a favorable efficacy and acceptable toxicity in HER2-negative advanced gastric cancer patients, and long-term follow-up is needed.