First-line treatment options for advanced gastric/gastroesophageal junction cancer patients with PD-L1-positive: a systematic review and meta-analysis

Background:Lately, many trials have paid much attention on the oncological outcomes of immunotherapy combined with chemotherapy as a first-line treatment. The authors perform a systematic meta-analysis to assess the efficacy and safety of programmed death 1 inhibitor plus chemotherapy for first-line treatment in advanced gastric/gastroesophageal junction cancer. Materials and methods:Literature search through major databases in English and Chinese: PubMed, Embase, Cochrane library, web of Science and CNKI updated on 10 March 2023. Randomized controlled trials were selected to investigate chemotherapy plus programmed death 1 inhibitor versus chemotherapy. Results:A total of 7 randomised controlled trials including 5788 participants were included. The overall survival (hazard ratio=0.79;95% CI: 0.74-0.85, P<0.01), progression-free survival (hazard ratio=0.72; 95% CI: 0.67-0.77, P<0.01) and objective response rate (risk ratio=1.24,95% CI: 1.18-1.31, P<0.05) were longer than chemotherapy alone in the pooled analysis. For subgroup analyses of overall survival, programmed death 1 inhibitors plus chemotherapy had a significant advantage in patients with combined positive score greater than or equal to 5, in Asia, in men and in those younger than 65 years (P<0.01), as were immune-mediated adverse events (odds ratio=8.86;95% CI: 1.26-62.47,P<0.05) and treatment-related grade 3-5 adverse events (odds ratio=1.40,95% CI:1.20-1.62, P<0.01). Conclusion:Programmed death 1 inhibitors plus chemotherapy have significant antitumour activity compared to chemotherapy alone. However, it is riskier in terms of toxicity than chemotherapy. The authors recommend programmed death 1 inhibitors plus chemotherapy as the optimal treatment regimen for patients with positive programmed death ligand 1 expression, in Asia, male and less than 65 years of age. More well-designed studies are needed to investigate the efficacy and safety of different immune plus chemotherapy drug doses and regimens.