New developments and standard of care in the management of advanced gastric cancer

Clin Res Hepatol Gastroenterol. 2024 Jan;48(1):102245. doi: 10.1016/j.clinre.2023.102245. Epub 2023 Nov 11.

Abstract

Advanced gastric adenocarcinoma is a common disease with a poor prognosis whose treatment has for decades been based on cytotoxic chemotherapy, including platinum salts in first-line, and taxane or irinotecan in second or later line. Recent years have seen the emergence of new drugs that have improved patient survival, such as trastuzumab in first-line for HER2-positive tumors, ramucirumab alone or in combination with paclitaxel in second-line, and trifluridine-tipiracil beyond the second-line treatment. More recently, two monoclonal antibodies have demonstrated their efficacy in combination with oxaliplatin-based first-line chemotherapy, nivolumab (anti-PD1) for PD-L1 CPS ≥5 tumors, and zolbetuximab for tumors overexpressing Claudin 18.2. In addition, regorafenib has been also showed effective in phase 3 trial for heavily pretreated patients. Based on phase 2 studies, trastuzumab-deruxtecan was approved in 2022 by the EMA for HER2-positive pretreated patients. This agent is currently evaluated in phase 3 study (DESTINY-Gastric04 trial), as are several other anti-HER2 (zanidatamab, margetuximab, tucatinib), immune checkpoint inhibitors, or targeted therapies (anti-FGFR2b).

Keywords: Drug combination; Immunotherapy; Molecular targeted therapy; Ramucirumab; Stomach neoplasms; Trastuzumab Deruxtecan; Trifluridine tipiracil.

Publication types

  • Review

MeSH terms

  • Antibodies, Bispecific*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Humans
  • Irinotecan / therapeutic use
  • Receptor, ErbB-2
  • Standard of Care
  • Stomach Neoplasms* / pathology
  • Trastuzumab / therapeutic use

Substances

  • zanidatamab
  • Trastuzumab
  • Irinotecan
  • Receptor, ErbB-2
  • Antibodies, Bispecific