Antiangiogenic therapies in gastric cancer: future directions for 2026 and beyond: an UNICANCER gastrointestinal group (UCGI) perspective.

Fiche publication

Date publication

juin 2026

Journal

Cancer treatment reviews

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BEN ABDELGHANI Meher , Pr GHIRINGHELLI François , Dr LAMBERT Aurélien

Tous les auteurs :
Raimbourg J, Abdelghani MB, Boige V, Botsen D, Carnot A, Coutzac C, Delaye M, De Sousa Carvalho N, Dos Santos M, Edeline J, Ghiringhelli F, Lambert A, Le Sourd S, Palmieri LJ, Pernot S, Samalin E, Smolenschi C, Vivier-Chicoteau J, Marion S, de la Fouchardière C

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/42385352

Résumé

Antiangiogenic therapies have been extensively investigated in advanced/metastatic gastric cancers, but also in neoadjuvant settings. The anti-Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) monoclonal antibody ramucirumab was the first antiangiogenic agent approved for HER2-negative metastatic gastric adenocarcinomas and remains a standard second-line treatment either alone or in combination with paclitaxel. Other VEGFR-targeting agents, such as the tyrosine kinase inhibitors (TKI) regorafenib and apatinib, have failed to demonstrate any survival benefit in the first-line settings, while providing modest improvements in pretreated patients, even when combined with Immune Checkpoint Inhibitors (ICI). Despite showing no significant benefit in Caucasian patients, apatinib has been approved in China for pretreated patients with advanced/metastatic gastric cancer. Dose-limiting toxicities, and the lack of robust predictive biomarkers for patients' stratification may both contribute to the limited efficacy of these multi-target tyrosine kinase inhibitors in gastric cancers. Several ongoing clinical trials mostly conducted in China suggest that new generation of antiangiogenic agents, particularly bispecific antibodies targeting both VEGF and Programmed Cell Death 1 (PD-1) or its ligand PD-L1, may offer greater efficacy with reduced toxicity. However, these promising preliminary data await mature overall survival results as well as clinical validation in the global population. Developing more effective drugs is closely linked to identifying reliable predictive biomarkers, which are crucial for guiding patients' selection, monitoring treatment response and optimizing therapeutic combinations and sequencing. Although several biomarker candidates have been explored, reliable predictors are still awaited. This review summarizes current evidence and explores the future of antiangiogenic agents in gastric cancers.