Perioperative immune checkpoint inhibitors combined with chemotherapy versus chemotherapy for locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis of randomized controlled trials

Background: Immunotherapy in combination with chemotherapy has been approved as an initial treatment strategy for unresectable advanced gastric cancer (GC). However, the efficacy of adding immunotherapy to perioperative chemotherapy in locally advanced resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) remains uncertain. Therefore, a meta -analysis of randomized controlled trials (RCTs) was performed to compare the effectiveness of perioperative immune checkpoint inhibitors (ICIs) plus chemotherapy versus chemotherapy alone in patients with locally advanced resectable GC/GEJC. Methods: A comprehensive search of online databases was conducted to identify RCTs published until November 30, 2023. Odds ratios (ORs) with 95% confidence interval (CI) were calculated for primary outcomes, including R0 resection rate, D2 lymphadenectomy, pathologic complete response (pCR), and treatment-related adverse events (TRAEs). Results: A total of 2718 patients from five RCTs (six reports) were included in the analysis. The pooled ORs of R0 resection rate and D2 lymphadenectomy demonstrated that combination therapy with ICIs showed no significant difference compared to chemotherapy alone. However, the addition of ICIs significantly improved pCR rates (OR = 3.43, 95 % CI 2.61 -4.50, p < 0.0001). There were no significant differences observed in the incidence of any grade TRAEs and grade 3 -4 TRAEs. However, ICIs combination therapy was associated with significantly higher incidences of any grade irAEs (OR = 4.03, 95 % CI: 2.70 -6.00, p < 0.0001), as well as grade 3 -4 irAEs (OR = 4.51, 95 % CI: 2.27 -8.97, p < 0.0001). Conclusions: This study represents the first meta -analysis to demonstrate that perioperative combination therapy with ICIs yields superior pCR rates for patients with locally advanced GC/GEJC compared to chemotherapy.