Key result
Concomitant use of proton pump inhibitors in patients with colorectal cancer treated with bevacizumab was associated with a lower objective response rate (25% vs 50%), although this difference was not statistically significant.
Why the study?
Hypertension may serve as a biomarker of efficacy in bevacizumab-treated patients, but whether blood pressure-controlling drugs influence bevacizumab efficacy remains unclear.
Does concomitant proton pump inhibitor use reduce bevacizumab-induced hypertension and therapeutic efficacy in patients with colorectal cancer treated with bevacizumab?
Cohort (n=58)
No
Does concomitant proton pump inhibitor use reduce bevacizumab-induced hypertension and therapeutic efficacy in patients with colorectal cancer treated with bevacizumab?
Absolute Event Rate: 25% vs 50%
p-value: p=0.138
Concomitant use of proton pump inhibitors may reduce both the incidence of bevacizumab-induced hypertension and the anti-tumoral efficacy of bevacizumab by inducing VEGF expression.
May warrant caution with PPIs in bevacizumab-treated colorectal cancer; leaves open any interaction for prospective confirmation.
BACKGROUND: In patients treated with bevacizumab, hypertension may be a biomarker of therapeutic efficacy. However, it is not clear whether drugs that control blood pressure influence bevacizumab's efficacy. In this study, we investigated drugs that may affect hypertension in bevacizumab-treated patients and examined the impact on the therapeutic effect. PATIENTS AND METHODS: We analyzed 3,724,555 reports from the third quarter of 2010 to the second quarter of 2015. All data were obtained from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) analysis. In this retrospective cohort study, we investigated a total of 58 patients diagnosed with colorectal cancer and treated for the first time with bevacizumab containing XELOX or mFOLFOX6 at The University of Tokushima Hospital between January 2010 and December 2015. The effect of the treatment was evaluated according to Response Evaluation Criteria in Solid Tumors version 1.0. Thereafter, the effect was confirmed using Gene Expression Omnibus (GEO) and cultured cells. RESULTS: There are few reports in FAERS of hypertension in patients treated with omeprazole on bevacizumab. Based on the chart review, patients who used proton pump inhibitors (PPI) had a lower response to treatment than those who did not (response rate: 25% vs 50%). Furthermore, experiments on GEO and cell lines suggested that induction of vascular endothelial growth factor (VEGF) gene expression by PPIs is the cause of the reduced therapeutic effect. CONCLUSION: PPIs prevent hypertension in bevacizumab-treated patients but may reduce bevacizumab's anti-tumoral effects by inducing VEGF expression.
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Yagi et al. (2020) conducted a cohort in Colorectal cancer (n=58). Proton pump inhibitors vs. No proton pump inhibitors was evaluated on Objective response rate (ORR) (p=0.138). Concomitant use of proton pump inhibitors in patients with colorectal cancer treated with bevacizumab was associated with a lower objective response rate (25% vs 50%), although this difference was not statistically significant.
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