High-Dose PPI Plus Aspirin Reduced Esophageal Cancer Risk

Combination therapy with a high-dose proton pump inhibitor and aspirin reduced the risk of progression to esophageal cancer in patients with Barrett esophagus.

The combined use of aspirin and a high-dose proton pump inhibitor (PPI) appears to offer protection against the development of esophageal cancer in high-risk individuals, according to new findings presented at the 2018 American Society of Clinical Oncology Annual Meeting (abstract LBA4008). This strategy reduced the risk of developing high-grade dysplasia or progression to malignancy, and delayed death from any cause in people with Barrett esophagus. 

Lead study author Janusz Jankowski, MD, PhD, Deputy Vice Chancellor, Royal College of Surgeons, Ireland and Consultant Clinical Adviser, National Institutes for Health and Care Excellence, UK, estimated that these outcomes could be delayed by using these simple, over-the-counter products. While esophageal cancer is relatively uncommon, it is challenging to treat and has a very poor prognosis, with a 5-year survival rate of about 19%. Esomeprazole given at 40 mg twice daily, combined with low-dose aspirin, was the most effective of four chemoprevention strategies investigated in this randomized trial.

However, while individuals suffering from heartburn should discuss their risk of Barrett esophagus with their doctor, they “should not self-medicate with these medications,” Jankowski said.

Jankowski noted that the magnitude of the overall benefits observed in their trial were somewhat surprising and greater than expected.

“More than 52,000 cases of esophageal adenocarcinoma occur each year, with 5-year survival less than 10%,” he said. “The increasing incidence of esophageal adenocarcinoma is probably related to the rise in gastroesophageal reflux, Barrett esophagus, and the associated inflammation.”

PPIs reduce acid reflux and aspirin reduces inflammation, so both may have chemopreventive properties, he noted.

Jankowski also pointed out that the United Kingdom has one of the highest rates of esophageal cancer in the world. He further added that “there’s nowhere in the world that’s got more esophageal adenocarcinoma than my home city of Glasgow. In fact, the cancer prognosis for people hasn’t achieved much improvement in 30 or 40 years.”

The phase III ASPECT study included 2,563 individuals who had ≥ 1 cm of Barrett esophagus at baseline and were negative for high-grade dysplasia or esophageal adenocarcinoma. Participants were randomized to one of four study groups: high-dose esomeprazole (80-mg daily), high-dose esomeprazole (300-mg daily) with low-dose aspirin, low-dose esomeprazole (40-mg daily), or 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 (precancer) (three combined events), and the analysis was adjusted for patient age and duration of Barrett esophagus.

The median follow-up was 8.9 years, and the investigators found that high-dose esomeprazole had a statistically significant benefit on the combined endpoint compared with standard-dose esomeprazole (P = .0459). The most effective regimen was high-dose esomeprazole with low-dose aspirin.

The 8-year survival rates were 90% vs 87% patients treated with for high-dose vs low-dose esomeprazole (P = .0459). However, this survival benefit was not observed until 7 years into the protocol.

There was no benefit to aspirin when compared with no aspirin in the primary analysis, but there was a weak effect when censored for prior NSAID use. Overall the treatment regimens were safe, with serious side effects reported in only 1% of patients.

Commenting on the study, Andrew Epstein, MD, an ASCO Expert from Memorial Sloan Cancer Center in New York City, agreed that “patients with Barrett esophagus should speak with their physicians” about using this combination to delay and/or mitigate progression to cancer. But he also emphasized that these recommendations do not apply to everyone with gastroesophageal reflux.

“I want to stress that these are patients with Barrett’s, and we have to be very careful not to extrapolate to other settings, such as patients with symptoms of reflux but without a diagnosis of Barrett’s,” he said.