Use of proton pump inhibitors (PPIs) is associated with shorter survival among patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab monotherapy, according to research published in JAMA Network Open.

Researchers observed shorter progression-free survival (PFS) and overall survival (OS) in pembrolizumab-treated patients with a history of PPI use.

However, patients with a history of PPI use did not have inferior PFS or OS if they received immune checkpoint inhibitor (ICI) therapy in combination with chemotherapy.

This retrospective study included 425 NSCLC patients with a PD-L1 tumor proportion score of at least 50%. All patients received either pembrolizumab monotherapy (n=271) or an ICI plus chemotherapy (n=154) as their first-line treatment. PPIs were used by 35% of patients in the monotherapy group and 25% of patients in the combination therapy group.

The median follow-up was 18.5 months. Among patients with a history of PPI use, the median PFS was 5.7 months in the monotherapy group and 19.3 months in the combination group (hazard ratio [HR], 0.38; 95% CI, 0.20-0.72; P =.002).

In patients without a history of PPI use, the median PFS was 10.6 months in the monotherapy group and 18.8 months in the combination group (HR, 0.81; 95% CI, 0.56-1.17; P =.26).

In patients with a history of PPI use, the median OS was 18.4 months in the monotherapy group and not reached in the combination group (HR, 0.43; 95% CI, 0.20-0.92; P =.03).

In patients without a history of PPI use, median OS was 29.9 months in the monotherapy group and not reached in the combination group (HR, 0.75; 95% CI, 0.48-1.18; P =.21).

In a multivariate analysis, the researchers found an independent association between PPI use and shorter PFS among patients treated with pembrolizumab monotherapy (HR, 1.38; 95% CI, 1.00-1.91; P =.048) but no such association in patients treated with ICI plus chemotherapy.

PPI use may be “an important clinical factor that should be considered in choosing treatment with ICI with or without chemotherapy in this population,” the researchers concluded. “Furthermore, when considering treatment strategies for patients in whom ICI plus chemotherapy is challenging, the appropriateness and necessity of PPI prescriptions should be assessed before initiating first-line treatment.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Kawachi H, Yamada T, Tamiya M, et al. Concomitant proton pump inhibitor use with pembrolizumab monotherapy vs immune checkpoint inhibitor plus chemotherapy in patients with non−small cell lung cancer. JAMA Netw Open. Published online July 11, 2023. doi:10.1001/jamanetworkopen.2023.22915