Background: Although immune checkpoint inhibitors (ICIs) have significantly improved treatment outcomes in select groups of cancer patients, they are limited by low response rates and high rates of immune-related adverse events (irAEs). Proton pump inhibitors (PPIs) have been suggested to worsen clinical outcomes in ICI recipients by altering the gut microbiome and disrupting downstream anticancer immune responses.
Aim: This project aimed to evaluate the impact of concomitant PPI use on the overall survival (OS), progression-free survival (PFS), irAE incidence and irAE severity in cancer patients receiving combination ipilimumab and nivolumab (ipi/nivo) immunotherapy.
Methods: A retrospective cohort study was conducted on patients who received ipi/nivo at Nepean Hospital between January 2021 and December 2025. Demographic and clinical data was collected from MOSAIQ and PowerChart. PPI use was defined as the administration of any PPI from ipi/nivo commencement up to 30 days after the final dose. Descriptive statistics and survival analysis was conducted to compare OS, PFS and irAE outcomes between PPI users and non-users.
Results: Of the 85 patients included in the analysis, 57 (67%) were PPI users. On multivariable Cox regression, PPI use was not associated with significant differences in OS (hazard ratio [HR] 1.86, 95% confidence interval [CI] 0.82-4.26, p=0.14) or PFS (HR 1.24, 95% CI 0.68-2.25, p=0.48). PPIs did not significantly affect the incidence of irAEs graded ≥2 (75% in PPI users vs 57% in non-users, p=0.085), the incidence of gastrointestinal irAEs (23% vs 14%, p=0.36), rates of hospitalisation for irAEs (49% vs 56%, p=0.61) or rates of ICI cessation (58% vs 56%, p=0.90).
Conclusions: While our study did not find significant associations between PPIs and survival or irAE outcomes, a trend towards poorer OS and irAE outcomes was observed. Further prospective studies are required to validate the relationship between PPIs and clinical outcomes in ICI recipients.