2174P - The impact of exposure to antibiotic (ATB) and proton pump inhibitor (PPI) therapy on immune checkpoint inhibitor (ICI) treatment on overall survival (OS): A population-based study

Background

PPIs and ATBs have been individually demonstrated to negatively impact ICIs outcomes due to their effects on the gut microbiome. However, many were smaller studies with heterogeneity in study design, ATB classes and exposure windows and few studies have studied both together. Here, we performed a population-level retrospective cohort study evaluating the impact of both PPI and ATB exposure prior to ICI on OS.

Methods

We used population-level administrative data to identify a cohort of cancer patients ≥ 65 years of age receiving ICIs from 06/2012 to 10/2018 in Ontario, Canada and deterministically linked with databases to obtain demographics, co-variates and PPI and ATB prescription claims. Patients were grouped as having PPI only (PPI+/ATB-), ATB only (PPI-/ATB+), both exposures (PPI+/ATB+), or neither (PPI-/ATB-) at 1 year and 60 days prior to ICI. Multivariable cox-proportional hazard models evaluated exposure both within 1 year and 60 days prior to starting ICI on OS, adjusted for age, gender, body mass index, comorbidities, autoimmune history, hospitalization in the past year and treatment facility level at start of ICI therapy.

Results

Among 2737 patients, median age 73; 43% received Nivolumab, 41% Pembrolizumab and 13% Ipilimumab; 53% had lung cancer, 34% melanoma. 59% and 19% of patients received any ATBs 1 year and 60 days before ICI therapy, respectively and PPIs 45% and 26% respectively. Median OS estimate was 306 days. Results at 1 year and 60 days are listed below. In ATB subclass analysis, exposure to both cephalosporins and PPIs within 60 days had the greatest impact on OS compared to PPI-/ATB- (aHR=1.76, 95% CI (1.23-2.48), p=0.002). Table: 2174P

Summary of association of ATB and PPI exposure on ICI outcomes in overall cohort

Conclusions

Exposure to PPIs and ATBs together prior to ICI therapy may be associated with worse OS than exposure to either alone. Interventions aimed at altering the gut microbiome may be required to help improve outcomes for patients on ICIs with prior PPI or ATB exposure.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

ASCO/Conquer Cancer Foundation, Canadian Association of Medical Oncologists.

Disclosure

P.L. Bedard: Financial Interests, Institutional, Local PI: AstraZeneca, Bicara, BMS, Amgen, Novartis, Genentech/Roche, Sanofi, Merck, Pfizer, Zymeworks, Nektar Therapeutics, Lilly, SeaGen, Medicenna; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Funding: Servier; Non-Financial Interests, Member of Board of Directors, Executive Board Member: Breast International Group; Non-Financial Interests, Leadership Role, Chair: AACR Project GENIE; Non-Financial Interests, Leadership Role, Past Chair IND CommitteeMember, Breast Site Steering Committee: Canadian Clinical Trials Group; Non-Financial Interests, Advisory Role: SeaGen, Lilly, Amgen, Merck, BMS, Pfizer, Gilead. G. Liu: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, Novartis, Lilly, Pfizer, Merck, EMD Serono, Jazz, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Takeda, AstraZeneca, EMD Serono. All other authors have declared no conflicts of interest.