Efficacy of the first-line immune checkpoint inhibitor plus chemotherapy for gastroesophageal cancer: A meta-analysis of phase III trials including unreported PD-L1 subgroups

The treatment paradigm for gastroesophageal cancers is evolving with immune checkpoint inhibitors (ICIs) as first-line therapy, making it crucial to understand their efficacy across patient subgroups, especially concerning PD-L1 expression. We performed a meta-analysis of Phase III randomized controlled trials targeting the effectiveness of ICIs with or without chemotherapy for advanced/metastatic HER2-negative gastroesophageal adenocarcinoma (GEA) or esophageal squamous cell carcinoma (ESCC). Kaplan-Meier (KM) curves of all-comer populations and subgroups according to reported PD-L1 cut-offs were extracted from published reports. Using KMSubtraction algorithm, unreported PD-L1 subgroup survival data were reconstructed by utilizing published KM survival curves. Thirteen first-line phase III RCTs involving 11,795 patients with GEA or ESCC were included. For GEA, ICI with or without chemotherapy showed longer OS in patients with PD-L1 combined positive score ≥1 (HR 0.77, 95 % confidence intervals [CI] 0.71–0.83 for ICI plus chemotherapy; HR 0.86, 95 %CI 0.75–1.01 for ICI alone) compared to chemotherapy alone, showing less benefits in low PD-L1 subgroups. ICI, with or without chemotherapy displayed survival benefits among PD-L1 tumor proportion score ≥1 % for ESCC (HR 0.62, 95 %CI 0.52–0.74 for ICI plus chemotherapy; HR 0.67, 95 %CI 0.54–0.84 for ICI alone) compared to chemotherapy alone. ICI combinations were similarly beneficial for Asian and global patients with GEA or ESCC. In conclusion, this meta-analysis, which includes unreported PD-L1 subgroups show benefit of ICIs with or without chemotherapy as a first-line treatment for advanced gastroesophageal cancers, particularly among patients with high PD-L1 expression.