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Meta-Analysis
. 2025 Jul 28:623:217718.
doi: 10.1016/j.canlet.2025.217718. Epub 2025 Apr 14.

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

Choong-Kun Lee  1 , Sejung Park  2 , Yaeji Lee  3 , Choa Yun  3 , Moonki Hong  4 , Chung Mo Nam  5 , Hyun Cheol Chung  1 , Sun Young Rha  6
Affiliations
Meta-Analysis

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

Choong-Kun Lee et al. Cancer Lett. .

Erratum in

Abstract

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.

Keywords: Esophageal squamous cell carcinoma; Gastroesophageal adenocarcinoma; Gastroesophageal cancer; Immune checkpoint inhibitor; Immunotherapy; Meta-analysis; PD-L1.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C-k.L. received honoraria from AstraZeneca, Servier, Dong-A ST, Boryung Pharmaceuticals, and Roche; consulting fees from Roche, and Daiichi Sankyo; and received research grants or supports from Ono Pharmaceuticals, Celltrion, Boryung Pharmaceuticals, GC Biopharma and Lunit Inc (outside the submitted work). S.Y.R. received grant/research support from MSD, Celltrion, Boehringer-Ingelheim, Eli Lilly, Taiho, Bristol-Myers Squibb, ASLAN, and Incyte and provided consultation for Daiichi Sankyo, MSD, Eli Lilly, Bristol-Myers Squibb, Eisai, and the Speaker's Bureau for Eli Lilly, Bristol-Myers Squibb, MSD (outside the submitted work). H.C.C. received grants/research support from Eli Lilly, GlaxoSmithKline, MSD, Merck-Serono, Bristol-Myers Squibb, Taiho, Amgen, Beigene, Incyte, and Zymework and honoraria from Merck-Serono and Eli Lilly and provided consultation for Taiho, Celltrion, MSD, Eli Lilly, Bristol-Myers Squibb, Merck-Serono, Gloria, Beigene, Amgen, and Zymework (outside of the submitted work). The other authors declare no conflicts of interest.

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