Concomitant administration of proton pump inhibitors significantly and negatively impacted progression-free survival, overall survival, and disease control rate in patients with metastatic gastroesophageal cancer treated with capecitabine, a study published in JAMA Oncology has shown.1

Capecitabine is an oral cytotoxic agent commonly used across cancer subtypes, including breast cancer and gastrointestinal cancers. Because gastric acid suppressants, such as proton pump inhibitors (eg, omeprazole and pantropazole), affect the absorption of some oral medications, researchers sought to determine if proton pump inhibitors impair capecitabine efficacy.

For the study, investigators analyzed data from 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer who participated in the phase 3 TRIO-013 trial, which evaluated the efficacy and safety of capetcitabine and oxaliplatin with or without lapatinib. Of those, 42.0% received concomitant proton pump inhibitors and were evenly distributed between treatment arms.

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Results showed that among patients treated with capecitabine plus oxaliplatin, those who received proton pump inhibitors had a 55% higher risk of progression or death (hazard ratio [HR], 1.55; 95% CI, 1.29-1.81; P <.001) and a 34% higher risk of mortality (HR, 1.34; 95% CI, 1.06-1.62; P =.04) compared with those not treated with proton pump inhibitors.

In addition, patients treated with proton pump inhibitors had a disease control rate of 83% vs 72% for those not given proton pump inhibitors (P =.02).

After adjusting for confounding factors, study further demonstrated significantly poorer progression-free survival (HR, 1.68; 95% CI, 1.42-1.94; P <.001) and overall survival (HR, 1.41; 95% CI, 1.11-1.71; P =.001) in proton pump inhibitor-treated patients.

Researchers also found that concomitant administration with proton pump inhibitors had a lesser effect on progression-free survival and overall survival among those treated with lapatinib; however, investigators observed a significant difference in overall survival (HR, 1.38; 95% CI, 1.06-1.66; P =.03) in multivariate analysis.


1. Chu MP, Hecht JR, Slamon D, et al. Association of proton pump inhibitors and capecitabine efficacy in advanced gastroesophageal cancer: secondary analysis of the TRIO-013/LOGiC randomized clinical trial. JAMA Oncol. 2016 Oct 13. doi: 10.1001/jamaoncol.2016.3358. [Epub ahead of print]