Biologics in combination with chemotherapy for gastric cancer: is this the answer?

Abstract

Gastric cancer (GC) continues to be a significant problem worldwide and is the third leading cause of cancer death. Armamentarium to treat GC whether it is potentially curable or metastatic (incurable) has changed little over the last decades with only two new agents being approved (trastuzumab and ramucirumab). Many relatively healthy patients after second-line therapy have limited and generally ineffective options. The recent The Cancer Genome Atlas analysis has uncovered four genotypes of GC; however, it is not sufficient to change our treatment strategies and more work needs to be done. The popular front-line regimen containing a platinum compound and a fluoropyrimidine is widely used for drug development and has worked well globally. Thus, this combination appears suitable for adding a biologic agent. The search for new classes of cytotoxics has almost stopped, but it is clear that cytotoxic therapy continues to contribute and it is here to stay. Biologic agents that modulate the immune system of the host appear promising along with many other biologics that can potentially inhibit signaling pathways that are often employed by GC cells. We will briefly describe the efforts that have targeted EGFR, mTOR, angiogenesis and MET pathways.

Keywords:

• biologic therapy
• chemotherapy
• gastric cancer
• treatment

Acknowledgements

N Charalampakis has been awarded a scholarship from the Hellenic Society of Medical Oncology. N Charalampakis and E Elimova contributed equally to this work. Both these authors are co-first authors.

Declaration of interest

The authors have received generous grants from the Caporella, Dallas, Sultan, Park, Smith, Frazier, Oaks, Vanstekelenberg, Planjery, and Cantu Families. From the Schecter Private Foundation, Rivercreek Foundation, Kevin Fund, Myer Fund, Dio Fund, Milrod Fund, and Multidisciplinary Grants from the University of Texas M. D. Anderson Cancer Center, Houston, USA. The authors are supported in part by the National Cancer Institute awards CA138671, CA172741, CA129926 (JAA) and P30CA016672 and used the Biostatistics Resource Group (RS, H-CC). J Ajani has been part of the advisory board and contracted research for Amgen, Novartis and Lilly. He has acted as advisory committee for Celgene, he has also been involved in contracted research for Genetech, Roche and Taiho, as well as consulting agreements for Lilly. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.