Intraperitoneal and intravenous paclitaxel plus S-1 and sintilimab as first-line treatment for gastric cancer with peritoneal metastasis: a single-arm phase 2 trial (DRAGON-09).

[BACKGROUND] First-line PD-1 blockade plus chemotherapy has shown significant clinical benefit in metastatic gastric cancer. This study aimed to evaluate the efficacy and safety of sintilimab and S-1 plus intraperitoneal and intravenous paclitaxel as first-line treatment for patients with gastric cancer peritoneal metastasis (GCPM), as well as exploratory predictive biomarker analysis.

[METHODS] We conducted a single-arm, phase 2 trial at a single centre in China between Jan 1, 2022, and Dec 31, 2023. Patients with laparoscopically confirmed GCPM were treated with sintilimab (200 mg IV on D1), S-1 (40-60 mg orally twice a day for D1-14), and paclitaxel (20 mg/m intraperitoneally and 50 mg/m IV on D1 and 8), in cycles every 3 weeks. The primary efficacy endpoint was overall survival (OS) rate at 1 year. This study is registered with ClinicalTrials.gov, NCT05204173.

[FINDINGS] 38 patients were included. The median progression-free survival was 14.6 months (95% CI: 10.8-not reached [NR]) and OS was 18.4 months (95% CI: 15.0-NR). The post-hoc analysis showed the objective response rate was 57.9% and disease control rate was 94.7%. The most common treatment-related adverse events were anemia, glutamic oxaloacetic transaminase elevated, and leukopenia. Longitudinal analyses of plasma circulating tumor DNA showed that low baseline human genome equivalent was associated with favorable OS.

[INTERPRETATION] First-line sintilimab and S-1 plus intraperitoneal and intravenous paclitaxel showed promising therapeutic efficacy in patients with GCPM.

[FUNDING] Natural Science Foundation of Shanghai, Shanghai Municipal Health Commission, National Science Foundation of China, and the Shanghai Hospital Development Center.