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Effect of Proton Pump Inhibitors on Response to Atezolizumab in Urothelial Cancer

By: Anna Nowogrodzki
Posted: Friday, October 30, 2020

Proton pump inhibitors seem to be associated with worse survival outcomes for patients with advanced urothelial cancer receiving the immune checkpoint inhibitor atezolizumab (but not chemotherapy), according to a recent study of pooled data from two IMvigor trials. Ashley M. Hopkins, PhD, of Flinders University in Adelaide, Australia, and colleagues published their findings in Clinical Cancer Research.

“The findings from this study suggest that non-critical proton pump inhibitor use needs to be approached very cautiously, particularly when an immune checkpoint inhibitor is being used to treat urothelial cancer,” stated Dr. Hopkins in an American Association for Cancer Research press release.

The study included 1,360 patients with advanced urothelial cancer. Patients were pooled from the IMvigor210 single-arm clinical trial (atezolizumab treatment) and the IMvigor211 phase III randomized clinical trial (atezolizumab vs. chemotherapy). The researchers analyzed the relationship between use of a proton pump inhibitor and overall or progression-free survival. Proton pump inhibitor treatment was counted if it was given between 30 days before and 30 days after the start of treatment: 471 patients (35%) received a proton pump inhibitor in that period.

Patients who received a proton pump inhibitor had significantly worse overall survival (hazard ratio = 1.5) and progression-free survival (hazard ratio = 1.38) than did those who did not. However, this effect was held only for patients on atezolizumab, not on chemotherapy. In the randomized trial, IMvigor211, proton pump inhibitors were associated with a decrease in the magnitude of atezolizumab’s benefit to overall survival. The overall survival treatment effect was 1.04 for patients who received proton pump inhibitors, but it was 0.69 for patients who did not.

The study is limited by being a retrospective and post hoc analysis. Future research might examine proton pump inhibitors' effect on additional immune checkpoint inhibitors or combinations of them. 

Disclosure: The study authors’ disclosure information may be found at

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