Comparative efficacy and safety of tislelizumab and other programmed cell death protein 1 inhibitors in first-line treatment of advanced gastroesophageal cancers: a systematic review and network meta-analysis

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BACKGROUND: Several programmed cell death protein-1 inhibitors are approved for the first-line treatment of advanced gastric/gastroesophageal junction cancer, including pembrolizumab, nivolumab and, more recently, tislelizumab. Since direct comparisons between these agents are lacking, advanced statistical modeling can be utilized to evaluate the relative efficacy and safety of tislelizumab compared with other first-line immunotherapy regimens in this indication. METHODS: A systematic literature review was performed to identify and summarize published randomized controlled trials investigating first-line treatments in adult patients with unresectable, locally advanced, or metastatic human epidermal growth factor receptor 2-negative gastric/gastroesophageal junction cancer. Relevant trials were synthesized using a Bayesian network meta-analysis; fixed-effect models were conducted for all analyses. The network meta-analysis base case used the intent-to-treat populations for tislelizumab + chemotherapy and placebo + chemotherapy from RATIONALE-305. RESULTS: Key comparators included nivolumab + chemotherapy (ATTRACTION-4, CheckMate 649), and pembrolizumab + chemotherapy (KEYNOTE-062, KEYNOTE-859). Tislelizumab + chemotherapy demonstrated similar efficacy compared with nivolumab + chemotherapy and pembrolizumab + chemotherapy for both overall survival and progression-free survival. Tislelizumab + chemotherapy was associated with significantly lower odds of grade ≥ 3 treatment-related adverse events compared with nivolumab + chemotherapy, and there were no statistically significant differences between tislelizumab + chemotherapy compared with pembrolizumab + chemotherapy. CONCLUSION: Overall, these analyses suggest that tislelizumab + chemotherapy is similarly efficacious to pembrolizumab + chemotherapy and nivolumab + chemotherapy, and is associated with a similar or lower incidence of grade ≥ 3 treatment-related adverse events in the first-line treatment of gastric/gastroesophageal junction cancer.

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