PPI use in Urothelial Cancer linked to higher mortality, finds study
The study published in Clinical Cancer Research, suggested in a retrospective analysis of clinical trials investigating the immune checkpoint inhibitor atezolizumab and atezolizumab vs chemotherapy in patients with urothelial carcinoma, that proton pump inhibitor use was associated with a significantly higher risk of death in patients treated with atezolizumab. It further emphasized that the use of proton pump inhibitors did not impact overall or progression-free survival in patients treated with chemotherapy.
PPI has been shown to affect the gut microbiome, possibly by a direct effect of stomach acid, which normally provides the main defense system against bacterial influx from food and oral bacterial flora. Previous studies have suggested an association between PPI use and community pneumococcal pneumonia, supporting the hypothesis that PPI may affect the functionality of the immune system.
The research, by Hopkins et al, analyzed patient data from the IMvigor210 (single-arm atezolizumab trial, n = 429) and IMvigor211 (phase III randomized trial of atezolizumab vs chemotherapy, n = 931) clinical trials. The data were pooled in a Cox proportional analysis assessing the association between the use of proton pump inhibitors and overall survival and progression-free survival.
Proton pump inhibitor use was defined as any proton pump inhibitor administration between 30 days prior and 30 days after treatment initiation.
On analysis, the following facts were highlighted.
- The researchers found that of the 1,360 participants, 471 (35%) received a proton pump inhibitor within the 60-day window.
- Proton pump inhibitor use was associated with significantly worse overall survival (hazard ratio [HR] = 1.52, 95% confidence interval [CI] = 1.27–1.83, P < .001) and progression-free survival (HR = 1.38, 95% CI = 1.18–1.62, P < .001) in patients treated with atezolizumab, but not in those treated with chemotherapy (P > .05).
- In the randomized cohort of IMvigor211, the overall survival treatment effect [HR (95% CI) of atezolizumab vs chemotherapy was 1.04 (0.81–1.34) for proton pump inhibitor users, compared to 0.69 (0.56–0.84) for proton pump inhibitor nonusers (P = .013). Similar associations were noted in the PD-L1 immune checkpoint 2/3 population.
The researchers observed that-
· Among patients with urothelial cancer treated with atezolizumab, those who used proton pump inhibitors had a 68% greater risk of death, a 47% greater risk of disease progression, and a 54% lower objective response rate those who did not use proton pump inhibitors.
· Among nonusers of proton pump inhibitors, those treated with atezolizumab had a 31% lower risk of death than patients treated with chemotherapy.
· This study suggests that proton pump inhibitor use may alter the magnitude of atezolizumab efficacy compared to chemotherapy
"Proton pump inhibitors are overused or inappropriately used in patients with cancer by up to 50%, seemingly from a perspective that they will cause no harm," The findings from this study suggest that noncritical proton pump inhibitor use needs to be approached very cautiously, particularly when an immune checkpoint inhibitor is being used to treat urothelial cancer." said lead study author Ashley M. Hopkins.
For the full article follow the link: Proton Pump Inhibitors May Affect Responses to Atezolizumab in Patients with Urothelial Cancer.