Neoadjuvant and adjuvant multimodality therapies in resectable esophagogastric adenocarcinoma

ABSTRACT

Introduction: Gastric and esophageal adenocarcinoma is a leading cause of cancer-related death globally. Surgery is the cornerstone modality for cure where feasible. Clinical studies over the past two decades have provided evidence for the use of perioperative chemotherapy and chemoradiotherapy to improve patient outcomes. However, there remains no global consensus in the optimal use of these therapies.

Areas covered: In this review, the authors summarize the latest evidence for perioperative multimodality therapy in resectable esophagogastric adenocarcinoma including the use of combination chemotherapy and targeted therapy containing regimens. In addition, the authors discuss some of the clinical and molecular biomarkers, such as PET imaging and microsatellite instability which can inform future practice and further clinical investigation.

Expert opinion: A multimodal approach has been proven to improve survival outcomes over surgery alone. Whilst there is no global standard of care for multi-modality therapies in resectable OG cancer, clinical trials are refining the use of chemotherapy and radiotherapy in the neoadjuvant and adjuvant settings. Further investigation is on-going to further optimize therapy and the integration of molecular targeted agents.

KEYWORDS:

• Gastric cancer
• esophageal cancer
• chemotherapy
• radiotherapy
• neoadjuvant
• adjuvant

Acknowledgements

The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Article highlights

• Several randomized phase III trials have confirmed a survival benefit with pre- and post operative chemotherapy or chemoradiotherapy in resectable esophagogastric adenocarcinoma.

• There is significant geographical variation in the use of adjuvant and neoadjuvant chemotherapy or chemoradiotherapy.

• FLOT (5FU, oxaliplatin, docetaxel) is now considered the reference perioperative chemotherapy regimen.

• HER-2 directed, anti-angiogenesis and immunotherapy are molecular therapies currently under investigation.

• Randomized head-to-head studies are evaluating whether chemotherapy or chemoradiotherapy is the superior neoadjuvant modality.

• Positron emission tomography is a promising imaging modality to optimize the use of neoadjuvant chemotherapy and chemoradiotherapy.

• Microsatellite instability is potential biomarker of poor response to neoadjuvant or adjuvant chemotherapy and further investigation is warranted.

This box summarizes key points contained in the article.

Declaration of interest

D Lau is the recipient of the Australasian Gastro-Intestinal Trials Group/Merck Clinical Research Fellowship. A Athauda has no interests to declare. I Chau has served on the advisory boards for AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly & Company, Five Prime Therapeutics, Merck Serono, Merck Sharp and Dohme, Pierre Fabre, Oncologie International and Roche. He has also received research funding from Eli Lilly and Company, Janssen-Cilag, Merck Serono and Sanofi Oncology. Finally, Ian Chau declares that he has received honoraria from Eli Lilly and Company. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London.