Pharmacotherapy for metastatic esophageal cancer: where do we need to improve?

ABSTRACT

Introduction: Esophageal cancer is a heterogeneous cancer comprised of differing cells of origin, molecular changes, and immune microenvironments. To date, most advances have been made in chemotherapy regimens where a one-size-fits-all approach is used. As a result, there remains a lack of tailored treatment options for such a heterogeneous cancer. This paper highlights the current standard of care treatment options as well as active areas of clinical research.

Areas covered: The authors review the key trials that have led to current standard of care treatment including pivotal chemotherapy and targeted therapy trials. The authors then discuss the current approved uses and future directions for immunotherapy.

Expert opinion: Current treatment options lack tailored treatment strategies based on the tumor’s biology. To date, approved targeted approaches only include HER2-directed and anti-VEGFR2 therapies. Furthermore, while immunotherapy treatment response is often durable, few clear predictive biomarkers for response have been identified. Future research should focus on characterizing additional molecular targets for therapeutic intervention and predictive biomarkers for immunotherapy, as well as combination approaches of immunotherapy with other therapeutic modalities to increase response rate. Ultimately, the field should strive to develop personalized treatment options based on a tumor’s molecular profile, microenvironment, and neo-antigen expression.

KEYWORDS:

• Cancer
• chemotherapy
• esophagus
• gastroesophageal junction
• metastatic
• sqamous cell cancer
• adenocarcinoma

Article highlights

• Esophageal cancer is the eighth most common cancer with an estimated 456,000 new cases worldwide in 2012. Fewer than 5% of patients with metastatic esophageal cancer survive beyond 5 years.

• Esophageal cancer is a heterogeneous cancer with differing cells of origin, molecular changes, and immune microenvironments. As a result, there are limitations in further improving clinical outcomes with standard one-size-fits-all chemotherapy regimens.

• Future treatment options should include tailored treatment approaches based on an individual’s tumor biology. Currently approved targeted approaches include HER2 directed therapy and anti-VEGFR2 therapy. Immunotherapy may have durable responses for a subset of patients with a PD-L1 proportion score ≥1% and dMMR esophageal cancer.

• Trials are ongoing to increase the response rates to immunotherapy by combining with other therapeutic modalities.

• Adoptive T-cell transfer technology is being investigated for the treatment of advanced esophageal cancer.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One referee declares research funding from Taiho Pharma, Ono Pharma, Bristol-Myers Squibb as well as honoraria from Taiho Pharma, Ono Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical Co., Eli Lilly and Company.

Additional information

Funding

This manuscript was not funded.