Neoadjuvant Therapy with Immune Checkpoint Inhibitors in Gastric Cancer: A Systematic Review and Meta-Analysis

Abstract

Background: Immune checkpoint inhibitors (ICIs) have shown great promise in treating late-stage gastric cancer, but their efficacy in the neoadjuvant setting has not been studied in large cohorts. Here, we explored the efficacy and safety of neoadjuvant ICI-based therapy in locally advanced gastric cancer.

Patients and methods: We included studies containing patients with locally advanced gastric/gastroesophageal cancer who received ICI-based neoadjuvant therapy. We searched PubMed, Embase, Cochrane library, and abstracts from major international oncology conferences. We performed this meta-analysis using the META package in R.3.6.1.

Results: Twenty-one prospective phase I/II studies comprising 687 patients were identified. The pathological complete response (pCR) rate was 0.21 (95% CI 0.18-0.24), major pathological response (MPR) rate was 0.41 (95% CI 0.31-0.52), and R0 resection rate was 0.94 (95% CI 0.92-0.96). The efficacy was highest with ICI plus radiochemotherapy, lowest with ICI alone, and in the middle with ICI and chemotherapy ± anti-angiogenesis. dMMR/MSI-H and PD-L1-high patients benefited more than pMMR/MSS and PD-L1-low patients. Grade 3 or higher toxicity rate was 0.23 (95% CI 0.13-0.38). These results exceeded those in trials of neoadjuvant chemotherapy, where the rate of pCR was 0.08 (95% CI 0.06-0.11), MPR was 0.22 (95% CI 0.19-0.26), R0 section was 0.84 (95% CI 0.80-0.87), and overall grade 3 or higher toxicity was 0.28 (95% CI 0.13-0.47) in 4800 patients across 21 studies.

Conclusions: In summary, the integrated results show promising efficacy and safety of ICI-based neoadjuvant therapy for locally advanced gastric cancer and support further investigation in large multicenter randomized trials.