Perspectives on the pharmacological management of esophageal cancer: where are we now and where do we need to go?

ABSTRACT

Introduction

Esophageal cancer (EC) represents a complicated heterogenous group of malignancies. ECs are divided broadly into two types, histologically: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Historically, EC study designs have used bucket type groupings (all subtypes and/or all gastroesophageal cancers) reducing contribution to developing precision oncology.

Areas covered

Surgery remains the curative modality for resectable disease with reasonable patient physiology. Trimodality is recommended for localized ESCC. An exception is cervical EC. For EAC, preoperative chemoradiation or perioperative chemotherapy is utilized. For those who undergo trimodality, nivolumab is recommended as an adjuvant therapy for those with a non-pathological complete response (pCR). Additionally, immunotherapy and other targets have been added to advanced EC treatment.

Expert opinion

Organ sparing approaches for localized tumors are starting to be investigated in many solid tumors and have been standard approaches for decades in certain tumors (i.e. certain head and neck tumors and anal SCCs). pCR differs between esophageal histologies with trimodality indicating potential of discriminating localized approaches. To determine if a watch and wait approach is feasible, prospectively correlating clinical complete response to pCR is needed, determining the best active surveillance strategy, and the best use of tools like liquid biopsies.

KEYWORDS:

• Esophageal neoplasms
• immunotherapy
• organ sparing
• nivolumab
• ipilimumab
• pembrolizumab
• human epidermal growth factor receptor-2
• fibroblast growth factor receptor
• claudin 18 isoform 2

Article highlights

• Esophageal cancer (EC) represents a complicated heterogenous group of malignancies divided broadly into two types, histologically: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC).

• Outcomes remain poor for those with localized or advanced disease.

• Patients with locoregional ESCC disease are commonly treated with trimodality therapy.

• Adjuvant nivolumab for one year to trimodality therapy is given for those with pathological residual disease after surgery.

• For EAC, preoperative chemoradiation or perioperative chemotherapy is utilized dependending on institution practice.

• Immune checkpoint inhibitor (ICI) approaches are being evaluated extensively in the localized setting.

• ICI has entered the front-line treatment for advanced ESCC and EAC patients through KEYNOTE-590, CHECKMATE 649, CHECKMATE-648, and KEYNOTE-811 along with other exciting targets.

• Organ sparing approaches are being evaluated in the solid tumor setting including esophageal tumors.

Declaration of interest

J. Ajani has disclosed: The University of Texas M. D. Anderson Cancer Center has received research grants on his behalf from BMS, Merck, Astellas, Taiho, Delta Fly, Roche, Prolinx, Zymeworks, Daiichi, Leap, Gilead, LaNova; he is a self-paid ad hoc consultant for BMS, Merck, Astellas, Taiho, More, Zymeworks, Beigene, Dava, AstraZeneca, Acrotech, Daiichi, Vaccinogen, Innovent, Merck Serono, Oncotherics, Bayer, OncLive, FivePrime, Amgen, GRAIL, Novartis, Geneos, Arcus, Servier, BI, Gilead. 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

This paper was not funded.