Late Breaking Abstract – ASCO 2018 Chemoprevention of Esophageal Cancer with NEXIUM® and Aspirin

SUMMARY: The American Cancer Society estimates that in 2018, about 17,290 new cases of esophageal cancer will be diagnosed in the US and about 15,850 individuals will die of the disease. It is the sixth most common cause of global cancer death. Squamous Cell Carcinoma is the most common type of cancer of the esophagus among African Americans, while Adenocarcinoma is more common in caucasians. In those with esophageal adenocarcinoma detected through symptoms, 5-year survival is less than 10%.

Barrett esophagus, defined as intestinal metaplasia in the distal esophagus, is a complication of GastroEsophageal Reflux Disease (GERD) and affects 2% of the adult population in western countries. In patients with Barrett’s esophagus, a portion of the esophagus that is usually lined with squamous epithelium undergoes metaplastic change to become columnar mucosa. Barrett esophagus predisposes patients to esophageal adenocarcinoma through a series of pathological events which include esophagitis, metaplasia, dysplasia and subsequently adenocarcinoma. Patients with Barrett’s esophagus are often screened for early malignancy with endoscopic evaluation with modest benefit. This is unlike screening for colorectal cancer that has proved successful in reducing colorectal cancer deaths.

It has been shown in observational studies that powerful acid suppression with Proton Pump Inhibitors (PPIs) could reduce risk of neoplastic progression in patients with Barrett’s esophagus, by downregulating cylcogoxygenase-2 expression. Esomeprazole (NEXIUM®) is the most commonly used PPI in the USA, and allows the healing of esophagitis without promoting clonal expansion of Barrett’s esophagus. Aspirin use in observational studies has been associated with reduced risk of esophageal adenocarcinoma. Based on these findings, the authors evaluated the efficacy and safety of these two drugs in the Aspirin and Esomeprazole Chemoprevention in Barrett’s metaplasia Trial (AspECT).

AspECT is a prospective, factorial design, multicenter, randomized, phase III study of chemoprevention by Aspirin and NEXIUM®, in patients with Barrett’s esophagus. Patients with Barrett’s esophagus of 1 cm or more (N=2557) were randomised 1:1:1:1 to Low-dose NEXIUM® (20 mg qd) and no Aspirin (N=705), High-dose NEXIUM® (40 mg bid) and no Aspirin (N=704), Low-dose NEXIUM® with Aspirin 300 mg qd (N=571) and High-dose NEXIUM® with Aspirin (N=577). The median follow up and treatment duration was 8.9 years. The Primary composite endpoint was time to all-cause mortality, esophageal adenocarcinoma, or high-grade dysplasia. The co-primary end points were the efficacy of High-dose PPI versus Low-dose PPI, and the efficacy of Aspirin versus no Aspirin.

It was noted that High-dose PPI was superior to Low-dose PPI (P=0.038). Aspirin was not significantly better than no Aspirin (P=0.068). However, if patients using Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) were censored at the time of first use, Aspirin was significantly better than no Aspirin (P=0.043). The most benefit was noted when High-dose PPI was combined with Aspirin compared with Low-dose PPI without Aspirin (P=0.0068). It appeared that the use of Aspirin and NEXIUM® (Proton Pump Inhibitor) would improve outcomes in Barrett’s esophagus, if given for at least 9 years. Serious adverse events were reported in only 1% of the participants.

It was concluded that in this largest randomized, controlled, chemoprevention trial in patients with Barrett’s esophagus, High dose NEXIUM® (given twice daily) along with Aspirin significantly reduces rates of death, esophageal adenocarcinoma, or high-grade dysplasia, with twice-daily NEXIUM® producing more effective suppression of acid reflux than once-daily dosing. Chemoprevention of esophageal cancer with esomeprazole and aspirin therapy: Efficacy and safety in the phase III randomized factorial ASPECT trial. Jankowski J, de Caestecker J, Love S, et al. J Clin Oncol 36, 2018 (suppl; abstr LBA4008)