Zanidatamab, a bispecific monoclonal antibody for HER2-positive gastro-oesophageal adenocarcinoma patients: a new hope?
Mené sur 46 patients atteints d'un adénocarcinome gastro-oesophagien HER2+ de stade avancé (durée médiane de suivi : 47,9 mois), cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité de l'ajout de zanidatamab (un anticorps bispécifique ciblant HER2) à une chimiothérapie de première ligne
Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) is a classical oncogene that was first shown to be actionable in breast cancer three decades ago. Its overexpression was first reported in gastro-oesophageal adenocarcinoma in 1986 and gained interest as a theragnostic biomarker in 2005.1 It is observed in 12–20% of cases, mainly in intestinal-type tumours and at the gastro-oesophageal junction.2 In gastro-oesophageal adenocarcinoma, HER2 3+ or 2+ confirmed by fluorescence in-situ hybridisation defines the target population. The monoclonal antibody trastuzumab, targeting the extracellular domain of the HER2 protein, was the first targeted therapy approved in combination with chemotherapy in first-line metastatic HER2-positive gastro-oesophageal adenocarcinoma based on the ToGA trial.3 In 2023, the randomised phase 3 KEYNOTE-811 trial evaluated the efficacy of adding pembrolizumab (anti-PD-1) to trastuzumab plus platinum-based chemotherapy in patients with untreated HER2-positive metastatic disease.4 Although dual primary survival endpoints were not met in the overall population, a significant survival outcome was reported in tumours co-expressing HER2 and PD-L1 (combined-positive score ≥1), representing the majority (85%) of HER2-positive cases, with ORR 73·2% (67·7–78·1), median progression-free survival 10·9 months (8·5–12·5), and overall survival 20·0 months (17·9–22·7).4 This led to the US Food and Drug Administration and the European Medicines Agency to approve the quadruplet regimen as the new first-line standard for gastro-oesophageal adenocarcinoma that is HER2-positive with a combined positive score for PD-L1 of one or above.
The Lancet Oncology , commentaire, 2025