Comparison of immune checkpoint inhibitors in combination with chemotherapy versus chemotherapy alone in the first-line treatment of advanced gastric cancer patients with low PD-L1 expression: a systematic review and meta-analysis.

ABSTRACT:

Background

Immune checkpoint inhibitors (ICIs) + chemotherapy became standard her2-GC first line treatment.

Objectives

The aim of this study is to investigate whether ICIs + chemo provides benefit for patients with low programmed death-ligand 1 (PD-L1) expression.

Design

This study is a systematic review and meta-analysis.

Data sources

We searched PubMed, Embase, Web of Science, and Cochrane Library as well as the 2019 to 2024 Annual Meetings of the European Society for Medical Oncology, the American Association for Cancer Research, the American Society of Clinical Oncology (ASCO), and the ASCO Symposium on Gastrointestinal Oncology (ASCO-GI) and the ClinicalTrials.gov database.

Methods

This systematic review included phase III randomized controlled trials comparing first-line immunotherapy combined with chemotherapy versus chemotherapy alone in advanced gastric cancer. KMSubtraction was used to estimate survival data for those trials that did not report data for the PD-L1 low-expression population.

Results

We included a total of nine randomized clinical trials. In patients with combined positive score (CPS) < 1 and CPS < 5, monoclonal antibody + chemotherapy did not show an improvement in overall survival (OS) or progression-free survival (PFS) (CPS < 1 OS: hazard ratio (HR) = 0.91, 95% CI: 0.77-1.08; PFS: HR = 0.88, 95% CI: 0.73-1.07. CPS < 5 OS: HR = 0.92, 95% CI: 0.79-1.08; PFS: HR = 0.78, 95% CI: 0.53-1.14). However, in trials using dual antibodies, patients with PD-L1 CPS < 5 achieved improvements in PFS (HR = 0.64, 95% CI: 0.52-0.80). In trials using tumor area positivity (TAP) scoring, the subgroup with TAP < 5% did not achieve benefits in OS or PFS from immunotherapy plus chemotherapy (OS: HR = 0.92, 95% CI: 0.75-1.13; PFS: HR = 0.91, 95% CI: 0.74-1.13).

Conclusion

Our study results indicate that in the first-line treatment of advanced gastric cancer, monoclonal antibody combined with chemotherapy does not provide a survival benefit compared to chemotherapy alone for patients with low PD-L1 expression. However, it is noteworthy that in the COMPASSION-15 trial, patients with CPS < 5 achieve significant improvements in OS and PFS, which may be related to the bispecific antibodies and needs to be validated by further studies.

Trial registration

This study was registered in PROSPERO (CRD42024568972).

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12062602 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature