Toripalimab combined with FLOT chemotherapy as conversion therapy for gastric cancer with peritoneal metastasis: a single-arm, open-label, phase II trial.

BACKGROUND: The combination of PD-1/PD-L1 monoclonal antibodies and chemotherapy has established a new standard of care for the first-line treatment of patients with unresectable locally advanced or metastatic gastric cancer (GC) and gastro-oesophageal junction adenocarcinoma. However, peritoneal metastasis represents a distinct pattern of dissemination in GC, typically associated with a poor prognosis. Whether the combination regimen improves survival for patients with concomitant peritoneal metastasis remains controversial. This study aims to evaluate the efficacy and safety of toripalimab (an anti-PD-1 monoclonal antibody) combined with FLOT chemotherapy as conversion therapy in these patients. METHODS: In this single-arm, open-label, phase II trial conducted in China, we enrolled patients aged 18–80 years with laparoscopically proven gastric cancer and peritoneal metastasis. Patients received toripalimab (3 mg/kg) plus FLOT chemotherapy (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2, 5-FU 2600 mg/m2) every 14 days for up to 4 cycles, followed by surgical resection. Patients who underwent surgery subsequently received 4 cycles of adjuvant treatment. The primary endpoint was the R0 resection conversion rate. The secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Between April 2021 and April 2023, 24 patients were screened, 20 of whom were included in this analysis. The median follow-up was 10.8 months. The objective response rate (ORR) was 35% and the disease control rate (DCR) was 80%. The R0 resection conversion rate after treatment was 25% (5/20), 40% (2/5) participants achieved TRG1 and 60% (3/5) participants achieved TRG2. The median PFS and OS were 6.5 and 10.8 months, respectively. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 35% of participants. CONCLUSIONS: Toripalimab combined with FLOT chemotherapy demonstrated potential conversion efficacy in the treatment of gastric cancer with peritoneal metastasis. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov (NCT04886193). Date of registration: 13 May 2021.