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Efficacy and Descriptive Safety Assessment of Programmed Cell Death Protein-(Ligand) 1 Inhibitors Plus Chemotherapy
Florian Lordick1, Efrat Dotan2, Lin Zhan3
1Department of Medicine II (Oncology, Gastroenterology, Hepatology, and Pulmonology), Comprehensive Cancer Center Central Germany, University of Leipzig Medical Center, Leipzig, Germany.
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.
