Published online Jul 26, 2021. doi: 10.12998/wjcc.v9.i21.5782
Peer-review started: February 10, 2021
First decision: March 30, 2021
Revised: April 13, 2021
Accepted: May 25, 2021
Article in press: May 25, 2021
Published online: July 26, 2021
The breakthrough of immune checkpoint inhibitor (ICI) therapy has created extensive opportunities for cancer immunotherapy. Especially, the block of programmed death-1/programmed death ligand 1 (PD-L1) axis using ICIs has become a new therapeutic strategy to treat advanced gastric cancer (GC). However, in the past decade, single-arm and randomized trials for single-drug ICI therapy showed that the therapeutic effect was not satisfactory, including clinical trials for advanced GC. However, after selecting suitable predictive biomarkers and developing a combination of anti-angiogenic targeted drugs and other chemotherapeutic drugs, the objective response rate and progression-free survival of patients with gastric cancer were improved significantly. The United States Food and Drug Administration has approved treatment with pembrolizumab for patients with advanced GC with PD-L1 expression or microsatellite instability-high/mismatch repair deficiency. In this review, the updated data from the latest trial results of combination immunotherapy for GC are presented. Based on the outcome of combination therapy, we discuss its possible molecular mechanism and summarize effective predictive biomarkers. We also discuss possible problems stemming from results of other clinical trials of ICI treatment and propose other directions for ICI therapy.
Core Tip: Immune checkpoint inhibitors gigantically expand the methods of immunotherapy and bring a glimmer of hopefulness for patients with advanced gastric cancer (GC). Ongoing clinical trials show that the effect of monotherapy was not satisfactory, while the combination therapy manifested a better response rate. The most recent clinical trial results of GC immunotherapy are reviewed to suggest the reasons and mechanisms of the high response rate. Additionally, we propose the potential problems of these trials and speculate on the benefits of immune checkpoint inhibitors in neoadjuvant therapy.