摘要
Alpha-fetoprotein-producing gastric or gastro-esophageal junction(AFP-G/GEJ)cancer,a rare gastric cancer subtype,exhibits increased angiogenesis and more immunosuppression than non-AFP-G/GEJ cancer.The potential benefits of anti-angiogenic agents and immunotherapy for this specific subtype remain unknown.This multi-center,single-arm,phase 2 trial(ClinicalTrials.gov NCT04609176)evaluated the antitumor activity,safety,and biomarkers of camrelizumab plus apatinib and S-1 and oxaliplatin(SOX),followed by maintenance treatment with camrelizumab plus apatinib,as a first-line treatment in patients with AFP-G/GEJ adenocarcinoma.Primary endpoint was the confirmed objective response rate(ORR)per RECIST v1.1 in the full analysis set.Secondary endpoints were disease control rate(DCR),progression-free survival(PFS),overall survival(OS),duration of response,time to response,and safety.Between December 4,2020,and August 4,2023,36 patients were enrolled and treated.The trial met its primary endpoint with a confirmed ORR of 66.7%(95%Cl:49.0-81.4).The DCR was 88.9%(95%Cl:73.9-96.9).With a median follow-up of 11.7 months(range:3.2-37.9),the median PFS reached 7.8 months(95%Cl:4.9-12.3)and the median OS reached 18.0 months(95%Cl:10.5-NR).No new safety concerns were identified.In exploratory analysis,patients with durable clinical benefit exhibited higher pre-treatment(PD-1+)CD8+T cell densities and effective scores.First-line treatment with camrelizumab plus apatinib and SOX,followed by maintenance treatment with camrelizumab plus apatinib,is effective and safe in AFP-G/GEJ adenocarcinoma.Further studies are necessary to validate these findings.
基金
Capital's Funds for Health Improvement and Research(2024-1-1021)
Beijing Natural Science Foundation(Z20J00105)
National Natural Science Foundation of China(82272627)
Beijing Natural Science Foundation(L234003)
the Beijing Xisike Clinical Oncology Research Foundation(Y-HR2020ZD-0773)。
