Perioperative chemoimmunotherapy for patients with gastric or gastroesophageal junction cancer: A systematic review and meta-analysis.

Abstract

430 Background: Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis, in combination with chemotherapy, are known to improve survival in advanced/metastatic gastric (GC) or gastroesophageal junction cancer (GEJC). Therefore, several trials incorporated ICIs in the neoadjuvant/peri-operative setting with promising preliminary results. The purpose of this meta-analysis was to determine the safety and efficacy of neoadjuvant chemoimmunotherapy for resectable GC or GEJC. Methods: PubMed/MEDLINE and Embase were systematically searched for randomized control trials (RCTs) investigating the efficacy of neoadjuvant anti PD-1/PD-L1 ICIs for locally advanced GC or GEJC up to 07/27/2024. Outcomes of interest were surgical outcomes such as pathological complete response (pCR) rate and major pathological response (MPR) rate. Risk ratio (RR) with 95% confidence intervals (CI) were pooled using a fixed model meta-analysis. Statistical analysis was performed with Review Manager 5.4.1. I² statistics was used to assess heterogeneity. The Cochrane risk of bias assessment tool was used to assess the risk of bias. All analyses were conducted at a significance level of 0.05. Results: Seven RCTs comprising 2,911 GC or GEJC patients were included. Among these, 1,454 patients received neoadjuvant chemoimmunotherapy and 1,457 patients received chemotherapy, respectively. Neoadjuvant chemoimmunotherapy significantly improved pCR rate (RR 2.94; 95% CI 2.34-3.70; P<0.00001; I 2 =33%), and MPR rate (RR 1.47; 95% CI 1.25-1.72; P<0.00001; I 2 =30%) compared to chemotherapy alone. Chemoimmunotherapy was associated with slightly higher incidence of grade 3 or worse treatment-related adverse events than chemotherapy (RR 1.07; 95% CI 1.01-1.14; p=0.03; I 2 =0%). Conclusions: This meta-analysis showed that adding ICIs to chemotherapy significantly improved the pCR and MPR rates and was feasible for patients with locally advanced GC or GEJC. Results of survival outcomes in the included trials and ongoing trials are awaited to further determine the efficacy and utility of chemoimmunotherapy and identify patient populations that benefit from this strategy. Included studies. Author Year Trial# Design Cancer; Stage Name of IO Target Chemo regimen Extracted data pCR MPR TRAE Ding X 2023 NCT04982939 P2 G/GEJ; Stage2-3 Sintilimab PD-1 SOX ○ ○ 　 Janjigian YY 2023 NCT04592913 P3 G/GEJ; ≥T2Nany/T0-4 N+ Durvalumab PD-L1 FLOT ○ 　 ○ Li C 2023 NCT04208347 P3 G/GEJ; T3-4aN+ Camrelizumab PD-1 SOX(+apatinib) ○ ○ 　 Lin JX 2024 NCT04195828 P2 G; T2-4N+ Camrelizumab PD-1 S-1+nabPTX ○ ○ ○ Lorenzen S 2024 NCT03421288 P2 G/GEJ; ≥T2 and/or N1 Atezolizumab PD-L1 FLOT ○ ○ 　 Peng Z 2024 NCT04661150 P2 G/GEJ HER2+; resectable Atezolizumab PD-L1 CAPOX+Tmab ○ 　 　 Shitara K 2024 NCT03221426 P3 G/GEJ; ≥T3N+ Pembrolizumab PD-1 FLOT or XP/FP ○ 　 ○ Yuan SQ 2024 NCT04250948 P2 G/GEJ; T3-4N+ Toripalimab PD-1 SOX/CAPOX ○ ○ ○