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

BACKGROUND: The addition of immune checkpoint inhibitors (ICIs) to perioperative treatment for resectable gastric or gastroesophageal junction (GEJ) cancers has shown promising results. However, current pivotal trials (KEYNOTE-585 and MATTERHORN) have reported conflicting survival outcomes. To clarify their therapeutic value, we conducted a meta-analysis evaluating the efficacy and safety of adding ICIs to this population. METHODS: PubMed, Embase, and major oncology conference abstracts were systematically searched for randomized controlled trials (RCTs) comparing ICIs plus chemotherapy versus chemotherapy alone in patients with resectable gastric or GEJ adenocarcinoma. Outcomes included pathological complete response (pCR), event-free survival (EFS), overall survival (OS), and treatment-related adverse events (TRAEs). Risk differences (RDs) and hazard ratios (HRs) were pooled using a fixed-effect model meta-analysis. RESULTS: Seven RCTs involving 2510 patients were included. Compared with chemotherapy alone, chemoimmunotherapy significantly improved pCR (17.6% vs. 6.1%; RD = 0.11, 95% CI = 0.09 to 0.14, P < .001), EFS (HR = 0.76, 95% CI = 0.66 to 0.86, P < .001), and OS (HR = 0.82, 95% CI = 0.71 to 0.94, P = .005). Subgroup analyses showed statistically significant efficacy in PD-L1 positive tumors, whereas no significant benefit was observed in PD-L1 negative patients. Grade ≥3 TRAEs were not significantly increased with chemoimmunotherapy (66.1% vs. 62.7%; RD = 0.04, 95% CI = 0.00 to 0.08, P = .08). CONCLUSIONS: The addition of ICIs to perioperative chemotherapy improves pathological and survival outcomes in resectable gastric or GEJ cancers, particularly in PD-L1 positive populations, without increasing grade ≥3 TRAEs. These findings support chemoimmunotherapy as a promising curative strategy.