Acid-suppressive agents and survival outcomes in patients with cancer: a systematic review and meta-analysis

Background: Patients with cancer often receive acid-suppressive agents (ASAs) to treat common gastroesophageal reflux and peptic ulcer diseases. Our systematic review addresses the association between ASAs and survival outcomes in these patients.

Methods: We searched MEDLINE, EMBASE, and Cochrane until December 2019, including randomized controlled trials (RCTs), quasi-RCTs, and observational studies concerning ASAs that reported progression-free survival (PFS) and/or overall survival (OS). We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) using the random-effects model, and assessed heterogeneity with I2 statistic.

Results: We included 45,626 patients from 7 RCTs and 18 observational studies, including esophageal/gastric, colorectal, pancreatic, lung, breast, prostate, kidney, and other cancers. Five studies showed that ASAs in lung cancer patients received tyrosine kinase inhibitors (TKIs) had significantly worse PFS (HR 1.64, 95% CI 1.14 – 2.37, I2 = 57%) and OS (HR 1.13, 95% CI 1.05 – 1.21, I2 = 0%) than nonusers. Each of five studies found no significant association between ASAs and OS in esophageal/gastric (HR 0.91, 95% CI 0.77 – 1.09, I2 = 32%) or colorectal cancer patients (HR 1.33, 95% CI 0.96- 1.85, I2 = 0%). ASAs were not significantly associated with an OS in patients with kidney cancer (HR 1.04, 95% CI 0.96 – 1.13, I2 = 28%).

Conclusions: Meta-analysis showed that ASAs significantly associated with an increased mortality risk in lung cancer patients treated TKIs, but not in patients with esophageal/gastric, colorectal, or kidney cancer. Until further studies confirm these results, caution should be used when administering ASAs and TKIs to patients with lung cancer.

Keywords: Acid-suppressive agent; Cancer; Histamine-2 receptor antagonists; Mortality; Proton pump inhibitors; Survival.