1065P - Dose dependent detrimental effect of baseline pantoprazole on clinical outcomes from first-line chemo-ICI regimens in patients with advanced stage NSCLC

Background

Several evidence indicates that proton pump inhibitors (PPIs) taken before immune checkpoint inhibitor (ICI) treatment may worsen outcomes in patients (pts) with solid tumors due to their gut microbiome disruptive effects. In NSCLC, the impact of PPIs in ICI-chemotherapy combos is debated, with no data on their potential dose-dependent effect.

Methods

Pts with advanced stage NSCLC treated with 1^st line chemotherapy plus pembrolizumab at the Fondazione Policlinico Campus Bio-Medico from Dec 2019 to Sep 2023 were included. Acknowledging the absence of mechanistic link between PPIs dosage and their detrimental effects we chose to limit the present analysis to pts receiving pantoprazole (PP) (the most prescribed PPI in our cohort), using non-PPIs pts as the control group. Data cut-off was March 2024. The main endpoints were overall survival (OS) and real-world progression-free survival (rw-PFS).

Results

Out of 134 pts, 101 (75.4%) were on PPIs at baseline. After the exclusion of 22 pts, the final population consisted of 112 pts with 16 (14.3%) and 63 (56.2%) of pts on 20 mg and 40 mg PP respectively. Treatment with PP was associated with the presence of CNS metastases (p=0.03) and with non-squamous histology (p=0.02). In addition, we reported a linear trend between increasing PP dose and concomitant corticosteroids treatment (12.2%, 31.2%, 54.0%, p<0.01). At the median follow-up was 26.9 months, PP 40 mg was associated with worse OS (HR 2.39, 95%CI: 1.34-4.29) and shorter rw PFS (HR 2.01, 95%CI: 1.22-3.29) compared to no-PPIs. Importantly, we found no significant difference between PP 20 mg and no PPIs. The multivariable analysis confirmed PP 40 mg as independent determinant of disease progression (HR 2.06, 95%CI: 1.16-3.63) and death (HR 1.94, 95%CI: 1.03-3.64). Interaction tests between PP and corticosteroids/PS ECOG, confirmed PP 40 mg exposure’s independent prognostic role.

Conclusions

Our results indicate a dose-dependent negative impact of baseline pantoprazole on NSCLC patients treated with ICI regimens. While these findings require validation in larger groups, they could inform clinical practice for potential adjustments in pts initiating chemo-ICI therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Cortellini: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, OncoC4, Ardelis Health, Access Infinity, AlphaSight; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai, Pierre Fabre; Financial Interests, Personal, Writing Engagement: MSD, BMS. All other authors have declared no conflicts of interest.