S Kordes1, A Cats2, S L Meijer3, H W M van Laarhoven4. 1. Department of Medical Oncology, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. Electronic address: s.kordes@amc.uva.nl. 2. Department of Gastroenterology, National Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. 3. Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. 4. Department of Medical Oncology, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
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.
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 carcinomapatients. Chemotherapy in combination with bevacizumab does not prolong survival in an unselected EGCpatient 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 EGCpatients.
Authors: Remy Klaassen; Ruben T H M Larue; Banafsche Mearadji; Stephanie O van der Woude; Jaap Stoker; Philippe Lambin; Hanneke W M van Laarhoven Journal: PLoS One Date: 2018-11-15 Impact factor: 3.240