Immunotherapy for oesophagogastric cancer

ABSTRACT

Introduction: Gastric and oesophageal cancers are a pressing global health problem with high mortality rates and poor outcomes for advanced disease. The mainstay of treatment in the palliative setting has traditionally been chemotherapy, which accrues only modest survival benefits. As with other cancer types, there is increasing interest in the use of immunotherapy approaches to improve outcomes.

Areas covered: This paper reviews the aetiological and genetic characteristics of oesophagogastric (OG) cancers relevant to the application of immunotherapy and outlines the historical, present-day and potential future applications of immunotherapy in their management.

Expert opinion: The use of agents targeting the PD1 pathway have led to impressive and durable responses in a minority of OG cancer patients and it would be expected that combinatorial approaches with chemotherapy, radiotherapy and other biological agents will improve responses further. Identification of clinically robust biomarkers is crucial in refining such approaches moving forwards. The application of modern sequencing technology to the development of personalized neoantigen-based vaccines represents an exciting amalgamation of genomics and immunotherapy, with potentially important clinical implications in OG cancer.

KEYWORDS:

• Immunotherapy
• gastric
• oesophageal
• cancer

Article highlights

• Immunotherapy including immune checkpoint inhibition is a growing area of research in gastric and esophageal cancers and certain epidemiological and molecular characteristics of these tumors may predict for favourable responses to immunotherapeutic approaches

• Checkpoint inhibition with the anti-PD1 monoclonal antibodies pembrolizumab and nivolumab have led to impressive response rates in advanced, heavily pre-treated gastric and esophageal cancer populations

• Responses have been seen in both PDL1 positive and negative patients however there is a trend towards higher response rates in tumors showing greater PDL-1 expression. Further biomarker research is required to effectively identify patients who will respond to immunotherapeutic approaches

• Combinatorial approaches of checkpoint inhibition alongside chemotherapy, radiotherapy and targeted agents are likely to further improve outcomes going forwards

• Modern sequencing technology now allows for the identification of unique, tumor-specific neoantigen profiles. Clinical trials applying this technology to tumor-unique neoantigen-based vaccines are ongoing and if successful would represent an exciting amalgamation of genomic technology and immunotherapy with potentially important implications for OG cancer treatment.

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Declaration of interest

I Chau is on the advisory board of Sanofi Oncology, Eli-Lilly and company, Bristol-Myers Squibb, Merck Sharp and Dohme, Merck Serono and Gilead Sciences. He has also received research funding from Janssen-Cilag, Sanofi Oncology, Roche, Merck Serono and Novartis and honoraria from Taiho, Pfizer Inc, Amgen Inc, Eli Lilly and company and Bayer Healthcare. 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.

Additional information

Funding

This paper has not been funded.