Combining chemotherapy, trastuzumab, and immune-checkpoint inhibitors in HER2-positive gastro-oesophageal cancer
Mené sur 698 patients atteints d'un cancer gastrique ou de la jonction oeso-gastrique HER2+ de stade localement avancé ou métastatique, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité de l'ajout du pembrolizumab à un traitement de première ligne combinant chimiothérapie à base de sels de platine et trastuzumab
HER2 overexpression or amplification occurs in 17–23% of gastro-oesophageal-adenocarcinoma tumours, driving oncogenesis. 1 , 2 The ToGA trial showed a survival advantage for trastuzumab, an anti-HER2 monoclonal antibody, with cytotoxic chemotherapy in HER2-positive (ie, IHC3-positive or IHC2-positive and fluorescence in situ hybridisation [FISH]-positive) advanced gastro-oesophageal adenocarcinoma. 3 Immune-checkpoint inhibition via anti-PD-1 antibodies and chemotherapy has improved survival in advanced, untreated gastro-oesophageal adenocarcinoma. The survival benefit from anti-PD-1 therapy is primarily confined to patients exhibiting tumour expression of PD-L1. 4 A majority of HER2-positive gastro-oesophageal-adenocarcinoma tumours co-express PD-L1, and preclinical models suggest synergy in dually targeting HER2 and PD-L1 axes.
The Lancet 2023