The efficacy and safety of PD-1/PD-L1 inhibitors plus chemotherapy versus chemotherapy alone in advanced or metastatic gastric or gastroesophageal junction cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: The combination chemotherapy of alpha-PD-1/PD-L1 has become the standard treatment option for some cancer patients. However, studies have shown that not all patients benefit from improved survival rates, especially the use of PD-1/PD-L1 inhibitors in combination with chemotherapy for progression-free survival (PFS) in patients with gastric or gastroesophageal cancer (GC/GEJC) remains highly controversial. To address this issue, we conducted a meta-analysis of randomized controlled trials (RCTs) aimed at comparing the efficacy of PD-1/PD-L1 inhibitors combined with chemotherapy versus chemotherapy in GC/GEJC patients.

METHOD: By searching relevant databases, RCTs published up to November 2024 were collected, and the hazard ratios (HR) and 95% confidence intervals (CI) of overall survival (OS) and PFS were calculated. Meanwhile, the odds ratios (OR) and 95% CI of treatment-related adverse events (TRAEs) were evaluated.

RESULT: A total of 6842 patients were included in seven trials. In the summary analysis of OS, compared with the chemotherapy group, the PD-1/PD-L1 inhibitor combined with the chemotherapy group showed significant improvement in OS (HR = 0.80; 95% CI = 0.76-0.85; p < 0.0001) and PFS (HR = 0.86; 95% CI = 0.71-0.81; p < 0.0001). Additionally, there were significant differences in the incidence of TRAEs (OR = 1.59; 95% CI = 1.21-2.02; p = 0.0001) and grade 3-4 TRAEs (OR = 1.43; 95% CI = 1.30-1.58; p < 0.0001).

CONCLUSION: When compared to chemotherapy, the combination of PD-1/PD-L1 inhibitors with chemotherapy improves survival but with higher toxicity risks, requiring careful benefit-risk evaluation in clinical practice.