2018 ASCO: Esomeprazole With Aspirin Offers Moderate Benefits in Patients With Barrett’s Esophagus

Key Points

  • High-dose esomeprazole had a statistically significant benefit on the combined endpoint compared to standard-dose esomeprazole.
  • The most effective treatment was high-dose esomeprazole with low-dose aspirin.
  • The treatments were safe overall, with serious side effects reported in only 1% of patients.

An updated analysis of a randomized phase III trial showed that taking a high dose of the acid-reducing medicine esomeprazole with low-dose aspirin for at least 7 years can moderately reduce the risk of developing high-grade dysplasia or esophageal cancer and delay death from any cause in people with Barrett’s esophagus. The findings were featured in a press briefing today and presented by Jankowski et al at the 2018 ASCO Annual Meeting (Abstract LBA4008).

The authors estimate that development of these adverse outcomes could be delayed by using these simple, over-the-counter medicines. Esophageal cancer is an uncommon cancer but very difficult to screen for and treat—fewer than 1 in 5 patients (19%) survive 5 years after diagnosis.

“Based on these data, we believe people with heartburn should talk with their doctor about their risk of Barrett’s esophagus, but they should not self-medicate with these medications,” said lead study author Janusz Jankowski, MD, PhD, Deputy Vice Chancellor, Royal College of Surgeons, Ireland; and Consultant Clinical Adviser, National Institute for Health and Care Excellence, United Kingdom. “We hope that the National Institute for Health and Care Excellence in the UK and national bodies in other countries will consider our findings when developing guidelines for esophageal cancer prevention.”

About Esophageal Cancer and Barrett’s Esophagus

Esophageal cancer accounts for only 1% of cancers diagnosed in the United States, but it is more common in other parts of the world. Esophageal adenocarcinoma is the most common type of esophageal cancer in the West, accounting for two-thirds of all esophageal cancers. Esophageal cancer is the seventh leading cause of death from cancer in the world. 

Barrett’s esophagus can develop in some people who have chronic gastroesophageal reflux disease or esophagitis, even when a person does not have symptoms of chronic heartburn. Damage to the lining of the esophagus causes the squamous cells in the lining of the esophagus to turn into glandular tissue. People with Barrett's esophagus are more likely to develop adenocarcinoma of the esophagus, but the risk of developing esophageal cancer is still fairly low.

It is estimated that Barrett’s esophagus occurs in only 2% of adults in Western countries, but some experts believe it may be underdiagnosed. Although people with this condition have a much higher risk for esophageal cancer compared to the general population, their absolute risk is still very small—the lifetime chance of developing the disease is only 2%.

It is estimated that 80% to 90% of esophageal cancers are preceded by Barrett’s esophagus, but most of the time, cancer is diagnosed before Barrett’s esophagus, because prior endoscopy has not been undertaken properly or at all. Prior research has suggested that acid reduction with standard-dose proton pump inhibitors might prevent the progression of Barrett’s esophagus to cancer. There is also evidence from observational studies that aspirin is effective in preventing gastrointestinal cancers, including esophageal cancer.

ASPECT Trial

The ASPECT trial randomly assigned 2,563 people with Barrett’s esophagus to 4 treatment groups:

  • High-dose proton pump inhibitor esomeprazole
  • High-dose esomeprazole with low-dose aspirin
  • Standard-dose (eg, low-dose) esomeprazole
  • Standard-dose (eg, low-dose) esomeprazole with low-dose aspirin

The primary endpoint was time to death from any cause, diagnosis of esophageal cancer, or diagnosis of high-grade dysplasia. The analysis adjusted for patient age and duration of Barrett’s esophagus.

Patients were followed for a median of 8.9 years, and high-dose esomeprazole had a statistically significant benefit on the combined endpoint compared to standard-dose esomeprazole (P = .0459). The most effective treatment was high-dose esomeprazole with low-dose aspirin.

Aspirin showed no benefit compared to no aspirin in the primary analysis. However, there was a weak effect when researchers censored for prior nonsteroidal anti-inflammatory drug (NSAID) use.

Safety Precautions

The treatments were safe overall, with serious side effects reported in only 1% of patients. Although both medicines are generally very safe, precautions should be taken before starting this regimen, noted Dr. Jankowski.

The most common side effect of proton pump inhibitors is diarrhea. People with heart disease should be aware that these drugs can interact with various heart medications. Other, much rarer risks include Clostridium difficile infection and osteoporosis.

The most serious side effects of aspirin include allergic reactions, bleeding in the stomach, and bleeding in the brain (particularly for people with hypertension). In addition, people who are already taking another NSAID should not be taking aspirin.

Next Steps

This was the largest chemoprevention randomized controlled trial in Barrett’s esophagus and it had the longest follow-up, but more research is needed, noted Dr. Jankowski. The research was conducted in only five countries with mostly white populations, so it is not known if this chemoprevention strategy would be as effective in black and Asian patients, as genetic ancestry can affect treatment efficacy. In addition, the researchers would like to follow patients on this study to see if 9 to 10 years of chemoprevention is even more effective and whether there is an increased risk for side effects with longer treatment.

Commentary

“The risk of esophageal cancer weighs on patients with Barrett’s esophagus. For these patients, this regimen reduces serious complications of acid reflux disease and the risk of dying from all causes, including esophageal cancer, and with little to no side effects. It’s an approach that people with Barrett’s should consider and discuss with their doctors,” said ASCO Expert Andrew Epstein, MD.

This study received funding from Cancer Research UK.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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