Efficacy and Descriptive Safety Assessment of Programmed Cell Death Protein-(Ligand) 1 Inhibitors Plus Chemotherapy as First-Line Treatment for Gastric and Gastroesophageal Junction Cancer in Asian and Non-Asian Patients: A Meta-Analysis.

BACKGROUND AND AIMS: Programmed cell death protein-(ligand) 1 (PD-[L]1) inhibitors have improved survival outcomes for patients with advanced gastric cancer (GC) or gastroesophageal junction cancer (GEJC). Given the higher incidence of GC mortality in Asian vs non-Asian populations coupled with some differences in etiology and treatment, this meta-analysis compared survival outcomes associated with first-line (1L) PD-(L)1 inhibitors plus chemotherapy in Asian and non-Asian patients with advanced GC/GEJC.

METHODS

A systematic literature review was undertaken to identify randomized, phase III studies examining efficacy and safety of 1L PD-(L)1 inhibitor plus chemotherapy treatment in patients with advanced GC/GEJC. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled using fixed and random effects models. Safety data were summarized descriptively.

RESULTS

Seven studies (3669 Asian and 3104 non-Asian patients) were included; 76% of patients had GC, ∼40% were aged ≥65 years, and 71% were male. PD-(L)1 inhibitors plus chemotherapy improved OS (HR, 0.80; 95% confidence interval [CI], 0.75-0.84) and PFS (HR, 0.75; 95% CI, 0.71-0.80) in the overall population. For the Asian and non-Asian regional breakdown, similar benefits were observed for OS (HR, 0.79; 95% CI, 0.73-0.85 and HR, 0.81; 95% CI, 0.74-0.89, respectively), with a comparable effect size for PFS (HR, 0.70; 95% CI, 0.64-0.76 and HR, 0.79; 95% CI, 0.70-0.89, respectively). Treatment-related adverse event rates were consistent across PD-(L)1 inhibitor plus chemotherapy (94%-98%) and placebo plus chemotherapy (92%-97%) groups.

CONCLUSION

1L PD-(L)1 inhibitors plus chemotherapy improved survival outcomes in patients with advanced GC/GEJC, regardless of Asian/non-Asian regional breakdown. These findings suggest that survival benefit is generalizable and independent of recruitment region.