Study Suggests PPIs Impact Efficacy of Pembrolizumab, H2RAs Do Not – Renal and Urology News

Patients receiving pembrolizumab for metastatic urothelial carcinoma may be better served by taking histamine-2 receptor antagonists (H2RAs) rather than proton pump inhibitors (PPIs), new research suggests.

Researchers found that metastatic urothelial carcinoma patients receiving pembrolizumab had significant reductions in progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) when they received PPIs.

H2RAs, on the other hand, did not appear to impact PFS, CSS, or OS in these patients. The researchers reported these findings in Clinical Genitourinary Cancer.

The study included 404 patients who had metastatic urothelial carcinoma treated with pembrolizumab. A total of 121 patients (29.9%) received PPIs, 34 (8.4%) received H2RAs, and 7 (1.7%) received both.

PPI recipients were significantly older than non-recipients (median ages, 73 and 72 years, respectively; P =.043), but there were no other significant differences in baseline characteristics according to PPI or H2RA use.

The median follow-up was 8.3 months. In the entire cohort, the median PFS was 9.1 months, the median CSS was 12.5 months, and the median OS was 11.4 months.

The median PFS was 6.4 months in patients who received PPIs and 9.7 months in patients who did not (P =.012). The median CSS was 8.6 months and 14.8 months, respectively (P =.018). The median OS was 7.8 months and 12.5 months, respectively (P =.010).

The median PFS was 9.1 months in patients who received H2RAs and 9.0 months in patients who did not (P =.9). The median CSS was 9.2 months and 13.1 months, respectively (P =.9). The median OS was 9.1 months and 11.5 months, respectively (P =1).

In multivariable analyses, PPI use was still associated with worse PFS (hazard ratio [HR], 1.35; 95% CI, 1.05-1.73; P =.020), CSS (HR, 1.45; 95% CI, 1.09-1.93; P =.011), and OS (HR, 1.42; 95% CI, 1.08-1.87; P =.011).

There were no significant associations between H2RAs and OS, CSS, or PFS in multivariable analyses.

The researchers suggested 2 possible mechanisms for the association between pembrolizumab efficacy and PPI use:

• Changes in gut microbiota diversity caused by PPIs may impact the efficacy of immune checkpoint inhibitors (ICIs)
• PPIs may suppress the immune system through anti-inflammatory effects by reducing the secretion of proinflammatory cytokines and adhesion molecules from inflammatory cells.

“Although we should take account of the gastrointestinal implications of not using PPIs, unnecessary use of PPIs should be avoided, and H2RAs can be an alternative during pembrolizumab treatment,” the researchers concluded.

They added, however, that additional studies are needed “to investigate the mechanism of the impact of H2RAs on ICIs and the feasibility and safety of H2RAs in ICI treatment instead of PPIs.”

This article originally appeared on Cancer Therapy Advisor