No Link Between Common Medication Use and ICI Efficacy, Study Finds

In a new observational study published in Cancer, commonly prescribed chronic medications did not affect the efficacy of immune checkpoint inhibitor (ICI) therapy in de novo metastatic non–small cell lung cancer (NSCLC), challenging prior findings in the literature.¹

The study was motivated by conflicting preclinical and clinical evidence regarding associations between ICI efficacy and use of common medications for comorbidity management. As most of the clinical studies were small and single-center, the authors set out to determine whether these reported associations reflected true pharmacologic effects or were instead a result of methodological bias or confounding.

To settle this uncertainty, the study employed a more robust, population-based comparative design. The study retrospectively identified 2 groups of patients with stage IV NSCLC from a large national cohort: those treated with first- or second-line ICI therapy (n = 3739) and those treated with chemotherapy (n = 6585) between 2005 and 2023, with the chemotherapy group serving as a control group.

Findings: No Impact on Oncologic Outcomes

Of 20 medication classes examined, 14 showed no association with overall survival (OS) or time to next treatment (TTNT) of patients treated with ICI therapy on propensity-weighted Cox regression analysis. While loop diuretics, anticoagulants, opioid analgesics, penicillin antibiotics, and fluoroquinolone antibiotics were associated with poorer OS (adjusted HR [aHR] range, 1.12–1.20) and TTNT (aHR range, 1.12–1.15), similar effects were observed in the chemotherapy group. Further, a higher immunomodulatory drug score also associated with worse outcomes, but this pattern was likewise seen in the chemotherapy group.

Given these findings, authors Brinzevich et al wrote, “Prior associations reported in the literature may be attributable to unmeasured confounding rather than true drug–immunotherapy interactions.”¹

Data Source and Study Cohorts

The study drew on electronic medical record data from the Veterans Health Administration (VHA) Corporate Data Warehouse, a national database containing information of all US veterans receiving care at VHA facilities. Outpatient Veterans Affairs pharmacy and inpatient medication administration records were used to obtain prescriptions for 20 commonly used medication classes.

The study included a total of 10,324 patients. The ICI group included patients who received ICI monotherapies with pembrolizumab (Keytruda) or nivolumab (Opdivo), or combination chemoimmunotherapy with pembrolizumab plus carboplatin/pemetrexed or carboplatin/paclitaxel. The chemotherapy group included patients who underwent platinum-based combination chemotherapy or monotherapy regimens including pemetrexed, docetaxel, gemcitabine, paclitaxel, or vinorelbine.

Study Limitations

The authors present several study limitations that warrant consideration when interpreting results. Although the study featured a comparator group to strengthen the internal validity of the findings, the study’s observational, retrospective nature still limits the ability to establish causality, and the lack of data on patient dietary and nutritional factors may have introduced potential residual confounding by related factors.

External validity is also a key consideration. The data source primarily encompasses a population of predominantly older male patients, potentially limiting generalizability to younger or female patients, and necessitates further confirmation in more diverse cohorts.

Other limitations mentioned by the authors included the potential for misclassification of concomitant medication exposure and the absence of assessments for other oncologic outcomes, such as objective response rate or radiographic progression-free survival.

Despite these limitations, the large national cohort and comparative design provide important further insights into the link between commonly prescribed medications and ICI efficacy in metastatic NSCLC, priming the foundation for continued research into comorbidity management with immunotherapy.

REFERENCES

1. Brinzevich D, Falvello V, Rehmani SS, et al. The effect of common medications on the efficacy of immune checkpoint inhibitors. Cancer. 2025;131(24):e70222-e70222. doi:10.1002/cncr.70222