Proton Pump Inhibitor Use and Survival Outcomes in Patients with Advanced Non-Small-Cell Lung Cancer Receiving...

Area of Science:

• Oncology
• Pharmacology
• Immunotherapy

Background:

• Immune checkpoint inhibitors (ICIs) improve survival in advanced non-small-cell lung cancer (NSCLC).
• Treatment responses to ICIs vary, prompting investigation into factors influencing efficacy.
• The impact of common medications like proton pump inhibitors (PPIs) on immunotherapy outcomes is increasingly scrutinized.

Purpose of the Study:

• To evaluate the association between PPI use and survival outcomes in advanced NSCLC patients receiving nivolumab.
• To investigate the influence of other common medications (metformin, statins, NSAIDs) on immunotherapy efficacy.
• To identify prognostic factors affecting progression-free survival (PFS) and overall survival (OS) in this patient cohort.

Main Methods:

• Retrospective cohort study of 179 advanced NSCLC patients treated with second-line nivolumab.
• Assessment of PPI, metformin, statin, and NSAID use within a 30-day window around nivolumab initiation.
• Survival analysis using Kaplan-Meier and Cox regression, with sensitivity analyses performed.

Main Results:

• PPI use was significantly associated with worse PFS (HR=2.22) and OS (HR=2.01) in multivariable analysis.
• Median PFS was 5 months for PPI users vs. 9 months for non-users (p<0.001); median OS was 9 months vs. 14 months (p=0.036).
• Metformin, statins, and NSAIDs showed no significant association with PFS or OS.

Conclusions:

• Proton pump inhibitor use is an independent adverse prognostic factor for PFS and OS in advanced NSCLC patients on nivolumab.
• These findings suggest a need to carefully reassess the necessity of PPIs during immunotherapy treatment.
• Further research may elucidate the mechanisms underlying PPIs' negative impact on ICI efficacy.