69P - Dose-dependent detrimental effect of proton pump inhibitors (PPIs) on clinical outcomes from immune checkpoint inhibitors (ICI) in patients (pts) with solid tumors

Background

PPIs taken before ICI may worsen outcomes in pts with solid tumors due to their gut microbiome disruptive effects, although no clear dose-dependent effect has been established yet.

Methods

We assessed the dose-dependent effects of PPIs on clinical outcomes in pts with stage IV solid tumors treated with PD-1/PD-L1 inhibitors at 17 Italian institutions from June 2014 to May 2020. PPI potency was standardized using the omeprazole equivalency (OE) method by Kirchheiner et al. An optimal OE cut-off was determined via the Youden index, categorizing pts into no PPI, low-potency PPI (≤13.5 mg/day OE), and high-potency PPI (>13.5 mg/day OE).

Results

Of the 675 pts included, 179 (26.5%) were on PPIs at baseline: 11.4% on low-potency and 15.1% on high-potency. Pts on PPIs were generally older, had poorer performance status (PS), higher disease burden, more baseline corticosteroid use, advanced-line treatment, and typically had non-small cell lung cancer. High-potency PPIs were associated with significantly worse overall survival (OS) (HR 1.55; 95% CI: 1.17-2.05) and progression-free survival (HR 2.02; 95% CI: 1.59-2.55) compared to no PPIs. Low-potency PPIs were not significantly associated with adverse outcomes. Multivariable Cox regression confirmed that only high-potency PPIs were associated with an increased risk of death (HR 1.55; 95% CI: 1.17-2.05), even after adjusting for potential confounders such as age, gender, PS, histology, disease burden, treatment line and baseline corticosteroid use. Double-adjusted propensity score matching confirmed the association between high-potency PPIs and poorer OS (HR 1.41; 95% CI: 1.04-1.92).

Conclusions

High-potency PPIs at baseline are associated with worse outcomes in pts treated with ICIs for stage IV solid tumors. Although further investigation is needed, these results suggest that PPIs should be used at the lowest effective dose to minimize potential detrimental effect.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.