<p>Effect of Immune Checkpoint Inhibitors Plus Chemotherapy on Advanced Gastric Cancer Patients with Elevated Serum AFP or Hepatoid Adenocarcinoma</p>

Abstract

Purpose Alpha-fetoprotein-producing gastric cancer (AFPGC) and hepatoid adenocarcinoma of stomach (HAS) are rare types of gastric cancer, with specific clinical manifestations and poor prognosis. The standardized treatment process of such cancers remains elusive. We aim to investigate the efficacy of immunotherapy combined with chemotherapy on patients with AFPGC or HAS. Patients and Methods AFPGC and HAS patients who underwent immunotherapy and/or chemotherapy as the first-line treatment at our institute from June 2016 to December 2018 were enrolled in this observational study. Their clinicopathological characteristics, serum AFP level and treatment methods were collected. The progression-free survival (PFS) and overall survival (OS) were analyzed and compared between patients who received immunotherapy plus chemotherapy and those received chemotherapy. Results A total of 21 patients with advanced AFPGC or HAS were included in the study and the median follow-up time was 28.0 months. Of the 21 patients, 7 patients received immunotherapy of PD-1 antibody (nivolumab) plus chemotherapy and 14 patients as control received chemotherapy with or without Herceptin/Apatinib. The median progression-free survival (mPFS) time was 5.0 months (4.3 months in the control group and 22.0 months in the immunotherapy group). The median overall survival (mOS) time of the control group was 16.0 months (14.0 months in chemotherapy alone subgroup, 20.0 months in chemotherapy plus Apatinib or Herceptin subgroup), while the mOS of patients receiving immunotherapy was not reached. Conclusion This study suggested PD-1 checkpoint inhibitor plus chemotherapy could benefit AFPGC and HAS patients. Its mechanism of action warrants further investigation.

Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer

“…The general ORR of chemotherapy in AFPGC was reported to be 8.3% to 66.7% as a first-line therapy, which is quite diverse among different reports because of the small sample sizes. A report of 7 advanced AFPGC patients treated with immunotherapy plus chemotherapy compared with 14 patients as control treated with chemotherapy with or without herceptin/apatinib as first-line treatment was published [28] . The median PFS was 22.0 months in immunotherapy group (4.3 months in control group).…”

A presumed extragonadal germ cell tumor that turned out to be a gastric cancer—a case report

“…Currently, there is no specific treatment for these special subtype, thus following treatment concepts of common gastric cancer (21). However, preliminary data suggest that patients with AFPproducing gastric cancer and hepatoid adenocarcinoma of the stomach may benefit from PD-1 checkpoint inhibitor combined with chemotherapy (21). In our case, systemic therapy with Capecitabine, Oxaliplatin and Trastuzumab was initiated based on positive IHC expression of HER2/ Neu and β-HCG.…”

“…AFP-positive gastric cancers can be classified into four subtypes including the hepatoid, yolk sac tumor, fetal gastrointestinal and mixed type (20). Currently, there is no specific treatment for these special subtype, thus following treatment concepts of common gastric cancer (21). However, preliminary data suggest that patients with AFPproducing gastric cancer and hepatoid adenocarcinoma of the stomach may benefit from PD-1 checkpoint inhibitor combined with chemotherapy (21).…”

Distinct molecular phenotype and the potential prognostic value of immune prognostic index and tumor infiltrating lymphocytes in hepatoid adenocarcinoma of stomach

“…Notably, GS and CIN GC are generally considered to have poor therapeutic response to ICIs treatment, however, ICIs combined chemotherapy seems to function well in the clinical practice of HAS treatment [11] . A portion of HAS patients with TP53+ status may be one of the plausible explanations for this particular phenomenon, and these patients would be likely to exhibit a good response to ICIs therapy.…”

“…attempted to identify the molecular characteristics and targets of HAS. Although these studies reported that most HAS patients had refractory malignancies with microsatellite stability (MSS) [ 5 , 7 ], favorable disease control from ICIs combined chemotherapy was observed [11] .These findings suggest that HAS is a genetically distinct subgroup of GC, and the reevaluation of molecular signatures and current protocols will contribute to a better understanding of the pathogenesis of HAS and development of precision therapies.…”