Management of early-stage gastro-esophageal cancers: expert perspectives from the Australasian Gastrointestinal Trials Group (AGITG) with invited international faculty

ABSTRACT

Introduction: A multimodal approach in operable early-stage oesophago-gastric (OG) cancer has evolved in the last decade, leading to improvement in overall outcomes.

Areas covered: A review of the published literature and conference abstracts was undertaken on the topic of optimal adjunctive chemotherapy or chemoradiotherapy in early-stage OG cancers. This review article focuses on the current evidence pertaining to neoadjuvant and perioperative strategies in curable OG cancers including the evolving landscape of immunotherapy and targeted drugs in this setting.

Expert commentary: Adjunctive therapies in the form of preoperative chemo-radiotherapy (CRT) or chemotherapy and perioperative chemotherapy over surgery alone improve outcomes in patients with operable OG cancer. Although there are variations in practice around the world, a multi-disciplinary approach to patient care is of paramount importance. Immunotherapy and on treatment functional imaging are two examples of emerging strategies to improve the outcome for early-stage patients. A better understanding of the molecular biology of this disease may help overcome the problem of tumor heterogeneity and enable more rationally designed and targeted therapeutic interventions in the future.

KEYWORDS:

• Gastric
• oesophageal
• adjuvant
• peri operative
• chemotherapy

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Article highlights

• Staging in esophageal and gastric cancer form the basis of the initial treatment decisions and should be done accurately. A major focus of staging is to exclude patients from receiving futile curative-intent surgery when they have more advanced disease that is not curable.

• Multimodal approach in the treatment of operable oesophagogastric cancer has improved survival compared to surgery alone.

• Overall 5-year survival rates remain <50% and further advances are needed to improve outcomes for these patients.

• Neoadjuvant CRT followed by surgery is the favored approach for patients with operable esophageal SCC whereas either perioperative chemotherapy or neoadjuvant CRT could be considered as standard options for operable esophageal adenocarcinoma.

• Definitive intent CRT in esophgaeal SCC has similar  survival outcomes however this is associated. Definitive CRT in esophageal SCC has similar survival outcomes however are associated with a higher risk of loco-regional recurrence. There is a lack of randomized head-to-head comparison between definitive CRT versus neoadjuvant CRT and surgery and as such definitive CRT is the current standard of care for patients who are medically unsuitable for oesophagectomy or refuse surgery.

• Perioperative chemotherapy remains the favored approach with FLOT being the recommended chemotherapy regimen in operable locally advanced gastric cancer in the Western population.

• Until recently, adjuvant chemotherapy has been the preferred approach in East Asian patients although this may change toward a perioperative/neoadjuvant approach based on the recent PRODIGY/RESOLVE studies presented in ESMO 2019.

• Until the results of TOPGEAR, CRITICS II and ESOPEC trials are reported the role of neoadjuvant CRT in gastric cancer patients is not established.

• Adjuvant (postoperative) CRT in select patients with gastric cancer is a reasonable option.

• There is an unmet need to establish predictive biomarkers of treatment response in early-stage disease and the role of targeted agents and immunotherapy is evolving in this setting.

• Enrollment to clinical trials with novel agents should be encouraged to enable identifıcation of patient populations who may benefıt from therapies that target specific molecular and immune pathways.

Declaration of interest

Ian Chau has served on the advisory board for: Eli-Lilly, Bristol Myers Squibb, MSD, Bayer, Roche, Merck-Serono, Five Prime Therapeutics, Astra-Zeneca, Oncologie International, and Pierre Fabre; received research funding from: Eli-Lilly, Janssen-Cilag, Sanofi Oncology, Merck-Serono; and has received honorarium from Eli-Lilly and Merck-Serono.

Florian Lordick has provided consulting and advisory services, speaking or writing engagements, public presentations for the following; Amgen, Astra Zeneca, Astellas, Biontech, BMS, Eli Lilly, Elsevier, Excerpta Medica, Imedex, Infomedica, Iomedico AG, Medscape, MedUpdate GmbH, Merck Sharp Dohme, Merck Serono, Oncovis Gmbh, Promedicis, Springer Nature Group, StreamedUp!, andZymeworks; and has received financial support from clinical trials or conducted research for Bristol Myers Squibb.

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 group meeting that enabled the material for this article to be assembled was supported by an unrestricted educational grant from Merck-Serono. The funding enabled travel for authors: Amitesh Roy, Timothy Price, Christos S Karapetis and Jeremy Shapiro. The funding also enabled honorariums for the international faculty: authors Florian Lordick, Li-Tzong Chen and Ian Chau.