GASTROINTESTINAL TRACT: Edited by Alain Hendlisz and Francesco SclafaniChanges in the therapeutic landscape of oesophago-gastric cancersFokter Dovnik, Ninaa; Smyth, Elizabeth C.bAuthor Information aUniversity Medical Centre Maribor, Maribor, Slovenia bCambridge University Hospitals NHS Foundation Trust, Cambridge, UK Correspondence to Elizabeth C. Smyth, MD, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK. Tel: +44 0 1223 245 151; e-mail: [email protected] Current Opinion in Oncology: July 2021 - Volume 33 - Issue 4 - p 362-367 doi: 10.1097/CCO.0000000000000728 Buy Metrics Abstract Purpose of review This article reviews recent randomised clinical trials on systemic treatment of oesophago-gastric cancers in the perioperative and metastatic setting. Recent findings 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. Summary 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. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.