Combining neoadjuvant chemotherapy with PD-1/PD-L1 inhibitors for locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis

Zhen Yuan; Hao Cui; Shuyuan Wang; Wenquan Liang; Bo Cao; Liqiang Song; Guibin Liu; Jun Huang; Lin Chen; Bo Wei

doi:10.3389/fonc.2023.1103320

Combining neoadjuvant chemotherapy with PD-1/PD-L1 inhibitors for locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis

Front Oncol. 2023 Jan 26:13:1103320. doi: 10.3389/fonc.2023.1103320. eCollection 2023.

Authors

Zhen Yuan^{1

2}, Hao Cui^{1

2}, Shuyuan Wang^{1

3}, Wenquan Liang², Bo Cao², Liqiang Song^{1

2}, Guibin Liu^{1

2}, Jun Huang^{1

2}, Lin Chen², Bo Wei²

Affiliations

¹ School of Medicine, Nankai University, Tianjin, China.
² Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
³ Department of Radiotherapy, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China.

Abstract

Background: Immune checkpoint inhibitors (ICIs) have shown promising prospects in locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) immunotherapy, but their efficacy in neoadjuvant settings remains unclear. This study aimed to assess the efficacy and safety of integrating programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors into neoadjuvant chemotherapy (NACT) of GC/GEJC treatment.

Methods: PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and main oncology conference databases were systematically searched up to 19 November 2022, and randomized controlled trials (RCTs) and cohort studies that evaluated the efficacy and safety of PD-1/PD-L1 inhibitors plus NACT were included. The main outcomes were pathological complete response (pCR), major pathological response (MPR), R0 resection rate, and treatment-related adverse events (TRAEs).

Results: A total of 753 patients from 20 prospective studies were included in this meta-analysis. The pooled pCR and MPR rates from studies reporting were 21.7% [95% confidence interval (CI), 18.1%-25.5%] and 44.0% (95% CI, 34.1%-53.8%), respectively. The pooled incidence rate of total TRAEs was 89.1% (95% CI, 82.7%-94.3%), and the incidence rate of grade 3 to 4 TRAEs was 34.4% (95% CI, 17.8%-66.5%). The pooled R0 resection rate was reported to be 98.9% (95% CI, 97.0%-99.9%). Subgroup analysis has not found significant differences in efficacy and safety among different PD-1/PD-L1 inhibitors. Moreover, the efficacy in patients with positive PD-L1 expression (combined positive score ≥1) was comparable with that in the entire study population [pCR, 22.5% vs. 21.2% (p > 0.05); MPR, 48.6% vs. 43.7% (p > 0.05)].

Conclusion: This systematic review and meta-analysis found that PD-1/PD-L1 inhibitors combined with NACT for locally advanced GC/GEJC were well tolerated and may confer therapeutic advantages. The integration of ICIs into NACT has shown the potential for application in any PD-L1 expression population.

Keywords: PD-1/PD-L1 inhibitors; gastric adenocarcinoma; gastroesophageal junction adenocarcinoma; immune checkpoint inhibitors; neoadjuvant immunotherapy.

Publication types

Systematic Review

Grants and funding

This work was supported by the National Basic Research Program of China (2019YFB1311505) and by the National Natural Science Foundation of China (82073192, 82273231). Beijing Science and Technology Program (Z221100007422125).