Targeted therapy for advanced esophagogastric adenocarcinoma

Crit Rev Oncol Hematol. 2014 Apr;90(1):68-76. doi: 10.1016/j.critrevonc.2013.10.004. Epub 2013 Oct 12.

Abstract

Background: Esophagogastric adenocarcinoma (EGC) is a molecular heterogeneous disease, and therefore, strategies with targeted therapy may be effective.

Aim: This review will discuss phase III studies in advanced EGC concerning biologic agents targeting molecular pathways, such as EGFR, HER2, VEGFR, mTOR and c-MET.

Results: HER2 inhibition with trastuzumab in combination with first line chemotherapy results in a significant survival benefit for HER2 positive carcinoma patients. Chemotherapy in combination with bevacizumab does not prolong survival in an unselected EGC patient cohort. Preliminary results of trials with EGFR, VEGFR and mTOR inhibitors are, thus far, disappointing in unselected patient cohorts. Promising studies in biomarker selected cohorts with HER2, EGFR and c-MET inhibitors are ongoing.

Conclusion: Targeted therapy in EGC is emerging. Improved insight in the biologic background of EGC is needed to improve patient selection, combine agents and discover new targets and agents. This may improve outcome for metastasized EGC patients.

Keywords: EGFR; Esophageal cancer; Gastric cancer; HER2; Targeted therapy; VEGFR; c-MET; mTOR.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Humans
  • Molecular Targeted Therapy*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology

Substances

  • Antineoplastic Agents