The use of proton pump inhibitors (PPIs) is associated with reduced efficacy of atezolizumab in patients with non-small cell lung cancer (NSCLC), according to research published in the Journal of Thoracic Oncology.

“Given approximately 30% of cancer patients use PPIs, there is an urgent need for evidence on the impacts of PPIs on other immune checkpoint inhibitors (ICIs) and for the development of guidelines on nonessential PPI use with ICIs,” the researchers wrote.

Previous studies suggested that ICI efficacy may be affected by gut dysbiosis, which can be caused by antibiotics or PPIs, the researchers noted. Because there is limited evidence from randomized controlled trials, the aim of the current study was to determine if antibiotic or PPI use affect atezolizumab efficacy in patients with NSCLC.

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The study included data from 4458 patients with advanced NSCLC who participated in 5 randomized controlled trials of atezolizumab (IMpower130, IMpower131, IMpower150, OAK, and POPLAR). 

In the overall cohort, 2723 patients were randomly assigned to treatment including atezolizumab. In this group, 194 patients had received an antibiotic within 30 days before starting atezolizumab, and 762 patients were taking a PPI on day 1 of atezolizumab treatment.

Of the 1735 patients randomly assigned to treatment without atezolizumab, 91 had received an antibiotic within the 30-day window, and 463 were taking a PPI on day 1 of study treatment.


The researchers found no significant association between antibiotic use within 30 days of starting treatment and overall survival (OS) or progression-free survival (PFS) among patients who received atezolizumab.

However, PPI use in the atezolizumab treatment group was significantly associated with worse OS (hazard ratio [HR], 1.23; 95% CI, 1.09-1.37; P <.001) and PFS (HR, 1.15; 95% CI, 1.03-1.28; P =.01) on adjusted analysis.

Among patients who did not receive atezolizumab, there was no association between PPI use and altered OS (HR, 1.01; 95% CI, 0.88-1.16; P =.87) or PFS (HR, 0.95; 95% CI, 0.81-1.12; P =.55).

In the pooled intent-to-treat population, PPI use was significantly associated with a decrease in the magnitude of OS benefit (P =.003) and PFS benefit (P =.03) with atezolizumab.

Based on these results, the researchers concluded that “PPI use is a clinical marker identifying reduced atezolizumab efficacy.” They added that, for patients without an appropriate indication for PPI use, stopping PPIs before the start of immune checkpoint inhibitor therapy “may be warranted.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Hopkins AM, Badaoui S, Kichenadasse G, et al. Efficacy of atezolizumab in patients with advanced non-small cell lung cancer receiving concomitant antibiotic or proton pump inhibitor treatment: Pooled analysis of five randomised control trials. J Thorac Oncol. Published online February 17, 2022. doi:10.1016/j.jtho.2022.02.003