Changes in the therapeutic landscape of oesophago-gastric cancers.

Abstract

This article reviews recent randomised clinical trials on systemic treatment of oesophago-gastric cancers in the perioperative and metastatic setting. Adding nivolumab to first-line chemotherapy improved survival in patients with metastatic gastric/gastro-oesophageal junction/oesophageal adenocarcinoma with PD-L1 combined positive score (CPS) ≥ five in a global trial and progression-free survival in metastatic gastric/gastro-oesophageal junction cancers in an Asian trial. The addition of pembrolizumab to first-line chemotherapy improved survival in metastatic oesophageal cancer patients, with the most benefit in oesophageal squamous cancer and tumours with high PD-L1 expression (CPS ≥ 10). Adjuvant nivolumab improved disease-free survival (DFS) in resectable oesophageal cancer patients with residual pathologic disease after neoadjuvant chemoradiation. In human epidermal growth factor receptor 2 (HER2)-positive oesophago-gastric adenocarcinoma, a phase II trial showed improved DFS when pertuzumab and trastuzumab were added to perioperative FLOT (5-fluorouracil/leucovorin, oxaliplatin, docetaxel). Another phase II trial showed improved response rates and survival in pretreated metastatic HER2-positive gastric and gastrooesophageal junction cancer patients who received the antibody-drug conjugate trastuzumab deruxtecan compared to physician's choice of chemotherapy. Chemo-immunotherapy combinations will become the new standard of care for some patients with metastatic oesophago-gastric cancers. Adjuvant nivolumab is a new option for oesophageal cancer patients with poor response after neoadjuvant chemoradiation.