Alpha-fetoprotein-producing gastric cancer (AFP-positive gastric cancer, AFP-GC), a rare and highly aggressive subtype of gastric cancer, accounts for 1.3% to 15% of all gastric cancer cases. Its clinical features are significantly different from those of common gastric cancer. Not only does it show abnormally elevated serum AFP levels, but it also has a stronger angiogenic ability, a higher rate of distant metastasis, and a poorer prognosis even after a upfront R0 surgery, making it a challenging problem in the field of gastric cancer treatment. Notably, patients with AFP-positive gastric cancer have a relatively low sensitivity to the traditional standard regimens. There is an urgent need to explore targeted treatment strategies to break through the efficacy bottleneck.
Combination of sintilimab, bevacizumab and XELOX/SOX for initially unresectable AFP-positive gastric/esophagogastric junction adenocarcinoma could be a novel therapeutic strategy to increase response rate and therapeutic efficacy. This study is a multi-center, single-arm phase 2 clinical trial to evaluate efficacy, tolerability and safety of perioperative sintilimab in combination with bevacizumab and XELOX/SOX in initially unresectable AFP-positive gastric/esophagogastric junction adenocarcinoma.
Signed informed consent;
Patients age 18-75 years;
Histologically CT/MRI confirmed cT3-4N+M0/1 gastric or GEJ adenocarcinoma; (M1 only includes type I liver metastasis of gastric cancer, according to the "Chinese Expert Consensus on Liver Metastasis of Gastric Cancer");
Serum AFP levels > 2× upper limit of normal or AFP-positive by IHC staining;
HER2-positive status: IHC 3+, or IHC 2+/FISH+
Prior chemotherapy, radiotherapy, anti-PD-1/PD-L1 therapy, surgery for gastric cancer;
Signs of other distant metastases (e.g., peritoneal, lung, bone, supraclavicular lymph, etc.)
Significant cardiovascular disease