The combination of anti-PD-1 antibodies, trastuzumab and chemotherapy may improve the outcome of some patients with HER2-positive alpha-fetoprotein-producing gastric cancer: a retrospective real-world analysis from a single center.

BACKGROUND: Patients with alpha-fetoprotein-producing gastric cancer (AFPGC) characterized with elevated serum AFP levels have received increased interest because of their aggressive behavior and poor prognosis. AFPGC patients who are HER2 positive are even poorer. METHODS: A single-center retrospective real-world analysis was conducted in patients with histologically confirmed gastric cancer, an AFP level > 7 ng/ml and who were pathologically HER2 positive at Tianjin Medical University Cancer Institute. Clinical characteristics, treatments and survival were recorded. The last follow-up date was February 10, 2023. The immune microenvironment was detected via multiple immunofluorescence stains. RESULTS: From May 2017 to May 2022, 29 advanced patients who were HER2 positive were included in the final analysis of 259 AFPGC patients. The median AFP level was 6745.13 ng/ml. Sixteen patients (61.5%) received the quadruplet combination of doublet chemotherapy, trastuzumab and anti-PD-1 antibody. The ORR and DCR were 66.7% and 91.7% in all patients, and 80% and 93.3% in patients in the quadruple combination group. The median progression-free survival (mPFS) and overall survival (mOS) for all patients were 10.27 and 20.50 months, respectively. For the quadruplet combination group, the mPFS and mOS were 7.47 and 14.87 months, respectively, but there were still 6 patients without disease progression and 8 patients who were alive (PFS and OS range: 7.3-41.07 months). Multiple immunofluorescence stains revealed significantly fewer CD3 + , CD8 + , CD56 + , and CD68 + immune cells in the tumor parenchyma and stroma in HER2-positive AFPGC patients than in HER2-negative and AFP-normal gastric cancer patients. CONCLUSIONS: Compared with current treatments, parts of HER2-positive AFPGC can achieve equivalent ORR and survival benefits, especially with HER2-targeted, anti-PD-1 antibody and chemotherapy.