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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2016; 22(8): 2403-2414
Published online Feb 28, 2016. doi: 10.3748/wjg.v22.i8.2403
Advanced gastric cancer: Current treatment landscape and future perspectives
Antonia Digklia, Anna Dorothea Wagner
Antonia Digklia, Anna Dorothea Wagner, Departement d’Oncologie, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
Author contributions: Digklia A performed the literature search and wrote parts of the manuscript; Wagner AD conceived the paper, wrote parts and revised the manuscript; both authors approved the final manuscript.
Conflict-of-interest statement: Digklia A has no conflict of interest to declare; Wagner AD has a consulting or advisory role for Roche, Merck, Celgene, Lilly, Bayer and been paid to participate in a speaker's bureau by Taiho. She is principal investigator of a study funded by Roche, and had travel costs paid by Merck, Bayer, Roche and Taiho.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Anna Dorothea Wagner, MD, Departement d’Oncologie, Centre Hospitalier Universitaire Vaudois, Bugnon 46, 1011 Lausanne, Switzerland. dorothea.wagner@.chuv.ch
Telephone: +41-21-3140155 Fax: +41-21-2140200
Received: April 30, 2015
Peer-review started: May 8, 2015
First decision: August 26, 2015
Revised: September 10, 2015
Accepted: November 24, 2015
Article in press: November 24, 2015
Published online: February 28, 2016
Abstract

Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease (locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2 (HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer.

Keywords: Gastric cancer, Phase III, Clinical trials, Chemotherapy, Targeted therapy, Perspectives

Core tip: With the integration of both ramucirumab and transtuzumab, treatment options for advanced gastric cancer have increased significantly in recent years. Therefore, a reconsideration of treatment options and results for gastric cancer is necessary. This paper discusses results of phase III trials for both standard chemotherapy and targeted treatments in metastatic gastric cancer. Furthermore, results of selected early-phase clinical trials, for example on immune checkpoint inhibitors, are discussed.