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Antacid, Aspirin Combination Slows Disease Progression in Barrett’s Esophagus
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CHICAGO — High-dose proton pump inhibitors in combination with low-dose aspirin may prevent the development of esophageal cancer among patients with Barrett’s esophagus, according to findings from the AspECT trial presented at the ASCO Annual Meeting.
People with Barrett's esophagus — which occurs among about 2% of adults in Western countries, although incidence may be underreported — are more likely to develop adenocarcinoma of the esophagus, although the risk for developing esophageal cancer is relatively low. Still, 80% to 90% of cases of esophageal cancer are preceded by Barrett’s esophagus.
“More than 52,000 cases of esophageal adenocarcinoma occur each year, with 5-year survival less than 10%,” Janusz Jankowski, MD, PhD, deputy vice chancellor of Royal College of Surgeons in Ireland and a consultant clinical adviser for the National Institutes for Health and Care Excellence in the U.K., said during a press conference. “The increasing incidence of esophageal adenocarcinoma is probably related to the rise in gastro-esophageal reflux, Barrett’s esophagus and the associated inflammation. Proton pump inhibitors reduce acid reflux and aspirin reduces inflammation — both may have chemo-preventative properties.”
Researchers of the AspECT trial evaluated the efficacy of the proton pump inhibitor esomeprazole plus aspirin for the prevention of esophageal adenocarcinoma among 2,563 patients with Barrett’s esophagus.
Researchers randomly assigned patients in a 1:1:1:1 fashion to 40 mg esomeprazole twice daily (high dose), 40 mg esomeprazole twice daily plus 300 mg aspirin daily, 20 mg esomeprazole once daily (low dose), or 20 mg esomeprazole once daily plus 300 mg aspirin daily.
Time to death from any cause and esophageal cancer or high-grade dysplasia diagnosis served as the study’s composite primary outcome.
At a median follow-up of 8.9 years, researchers observed a statistically significant delay in time to the composite endpoint with high-dose esomeprazole vs. low-dose esomeprazole (time ratio [TR] = 1.27; 95% CI, 1.01-1.58).
The combination of low-dose aspirin plus high-dose esomeprazole demonstrated the strongest delay of disease progression compared with low-dose esomeprazole alone (TR = 1.59; 95% CI, 1.14-2.23).
Researchers observed a trend with aspirin vs. no aspirin, but it did not reach statistical significance (TR = 1.24; 95% CI, 0.98-1.57).
Overall, the researchers estimated these interventions prevented 20% to 25% of esophageal cancers and delayed diagnosis of esophageal cancer by 1 to 2 years among those ultimately diagnosed.
Also, taking the medicines for at least 7.5 years had the greatest effect, whereas treatment for less than 4 years had no effect.
Serious adverse events occurred among 1% of patients.
“Although this was the largest chemoprevention randomized controlled trial in Barrett’s esophagus and with the longest follow-up, more research is needed,” Jankowski said. “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 people, as genetic ancestry can affect treatment efficacy.” – by Jennifer Southall
Reference:
Jankowski J, et al. LBA4008. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: The study was funded by the Cancer Research UK. Jankowski reports honoraria from and speaking roles with Teueda, as well as research funding from AstraZeneca. Please see the abstract for all other author’s relevant financial disclosures.
Perspective
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John C. Lipham, MD
I would caution people in how these data are interpreted; the conclusions that the researchers make in their abstract is the combination of high-dose proton pump inhibitor plus aspirin will prevent cancer. This is not exactly what the data state.
The data do state that high-dose proton pump inhibitor with aspirin leads to a slower progression to high-grade dysplasia compared with low-dose proton pump inhibitor with no aspirin. Unfortunately, the researchers grouped the patient cohort into four groups all four groups received sort of proton pump inhibitor, and two of the four groups had aspirin added to the regimen. What is lacking in this study is a control group, such as patients with Barretts esophagus not treated with anything.
There has been some recent data that suggest there is an association with patients who are taking proton pump inhibitors and a higher risk for the development of esophageal cancer in Barretts esophagus progressing to dysplasia or esophageal cancer. This study suggests that the risk is lower among people on high-dose proton pump inhibitor with aspirin. This, in fact, may be true, but the risk may still be higher than for patients not taking anything.
Another thing that the researchers did not do in this study is include a group that was just on aspirin.
Although this was a well-done study, the lack of a control arm or an aspirin-only arm limits the conclusion.
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Manish Shah, MD
Barrett’s esophagus, which is increasing in frequency, is the main risk factor for esophageal cancer. Esophageal cancer is deadly, with a median survival of less than 1 year. Many patients, even after surgery, have disease recurrence, and the cure rate is around 25%. So, anything that we can do to prevent the disease is helpful.
This abstract is written as a positive study; however, the challenge is that when there is high-grade disease, it is eminently treatable and curable. That there is a modest benefit in this composite endpoint of proton pump inhibitor and aspirin therapy did not change this.
Does this translate to reduced esophageal deaths? Researchers showed that the use of proton pump inhibitor was associated with reduced all-cause death, but that may be due to other benefits of proton pump inhibitor use, not specific to esophageal cancer.
These studies are hard to conduct and this is not a definitive result. There may be benefit to reducing inflammation in the esophagus and stomach, but the real message is that patients with reflux and heartburn should definitely be on proton pump inhibitor. We need to identify which patients should be screened beyond Barrett’s disease to identify disease early on.
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