1465P - Clinical impact of proton pump inhibitor on the therapeutic outcome of non-small cell lung cancer patients with PD-L1 TPS ≥50% receiving pembrolizumab monotherapy versus immune checkpoint inhibitor plus chemotherapy: A retrospective multicenter cohort study

Background

Pembrolizumab monotherapy and immune checkpoint inhibitor plus chemotherapy (ICI/Chemo) have been approved as first-line treatment for non-small cell lung cancer (NSCLC) with programmed death ligand 1 tumor proportion score (PD-L1 TPS) ≥50%. However, the clear distinction between the two therapeutic options remains unclear. It was reported that using proton pump inhibitors (PPI) and antibiotics correlated with poorer treatment outcomes of ICI monotherapy for NSCLC.

Methods

We retrospectively enrolled consecutive PD-L1 TPS ≥50% advanced NSCLC patients who received pembrolizumab monotherapy or ICI/Chemo as first-line treatment. We analyzed the association between treatment outcome and patient characteristics, including concomitant drug history in each group. Comparing the treatment outcome, propensity score matching was used to reduce bias.

Results

The study included 425 patients, with 271 receiving pembrolizumab monotherapy and 154 receiving ICI/Chemo. According to the multivariate analysis, a history of PPI usage was independently associated with shorter progression-free survival (PFS) in pembrolizumab monotherapy group(hazard ratio (HR): 1.38, 95.0% CI: 1.00–1.91; P = 0.048), but not in ICI/Chemo group (HR: 0.83, 95.0% CI: 0.48–1.45; P = 0.515). In patients with a history of PPI, both the median PFS (19.3 months vs. 5.7 months, P=0.002) and the median overall survival (OS) (not reached vs. 18.4 months, P=0.025) were significantly longer in ICI/Chemo group than in pembrolizumab monotherapy group. In patients without a history of PPI, the median PFS (18.8 months vs. 10.6 months, P=0.259) and the median OS (not reached vs. 29.9 months, P=0.211) was not significantly different between each group.

Conclusions

History of PPI usage was negatively associated with treatment outcome of pembrolizumab monotherapy, but not ICI/Chemo in NSCLC patients with PD-L1 expression ≥50%. Our observations in real-world settings suggest that the history of PPI usage may be a predictive clinical factor to be considered in treatment decision-making in this population.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.