Evidence map›Paper›PMID 41390939›Full record

ArticleCancer2025

The effect of common medications on the efficacy of immune checkpoint inhibitors.

Daria Brinzevich, Virginia Falvello, Sadiq S Rehmani, Garth W Strohbehn, Nithya Ramnath, Michael P Dykstra, Luke M Higgins, David Elliott, Matthew J Schipper, Michael D Green and 1 more

Erratum issuedAbstract read
In one paragraph

Article in Cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Daria BrinzevichDivision of Hematology/Oncology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Virginia FalvelloDivision of Hematology/Oncology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Sadiq S RehmaniDivision of Hematology/Oncology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Garth W StrohbehnDivision of Hematology/Oncology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Nithya RamnathDivision of Hematology/Oncology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Michael P DykstraDepartment of Radiation Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, USA.ORCID https://orcid.org/0000-0003-0834-7669
Luke M HigginsDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.ORCID https://orcid.org/0000-0002-4003-8535
David ElliottDepartment of Radiation Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, USA.
Matthew J SchipperDepartment of Radiation Oncology, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, USA.
Michael D GreenAnchorage Radiation Oncology Center, Anchorage, Alaska, USA.ORCID https://orcid.org/0000-0003-4951-7118
Alex K BryantVeterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan, USA.ORCID https://orcid.org/0000-0003-0194-8381

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMedications such as proton pump inhibitors (PPIs), antihistamines, and nonsteroidal anti-inflammatory drugs have been linked to immune checkpoint inhibitor (ICI) efficacy in patients with non-small cell lung cancer (NSCLC), but these associations may reflect unmeasured confounding rather than true pharmacologic effects. This study evaluated whether commonly prescribed medications influence ICI outcomes, using a national patient sample and a negative control cohort.

methodsThe authors identified Veterans Health Administration (VHA) patients with stage IV NSCLC treated with first- or second-line ICI therapy (n = 3739) or chemotherapy (n = 6585) from 2005 to 2023. Baseline use of 20 common medication classes and an immunomodulatory drug score were assessed. Propensity-weighted Cox regression evaluated associations between each medication class and overall survival (OS) or time-to-next treatment (TTNT) in the ICI group. For any medication with a nominally significant association (p < .05), the same analysis was repeated in the chemotherapy group to test for nonspecific effects.

resultsAfter propensity weighting, 14 of 20 medication classes showed no association with OS or TTNT in the ICI cohort. Loop diuretics, anticoagulants, opioids, penicillin antibiotics, and fluoroquinolone antibiotics were associated with worse outcomes, but similar effects were seen in the chemotherapy group. A higher immunomodulatory drug score was also associated with inferior outcomes among ICI patients, but this association was likewise present in the chemotherapy cohort.

conclusionIn this study, commonly prescribed medications did not appear to alter ICI efficacy in stage IV NSCLC. Prior associations reported in the literature may be attributable to unmeasured confounding rather than true drug-immunotherapy interactions.

Indexed as

Carcinoma, Non-Small-Cell LungImmune Checkpoint InhibitorsLung NeoplasmsAgedAnti-Inflammatory Agents, Non-SteroidalFemaleHistamine AntagonistsHumansMaleMiddle AgedProton Pump InhibitorsTreatment OutcomeUnited StatesAnti-Inflammatory Agents, Non-SteroidalHistamine AntagonistsImmune Checkpoint InhibitorsProton Pump Inhibitorscarcinomaimmune checkpoint inhibitorsimmunotherapylung neoplasmsnon‐small‐cell lungVeterans Health

Identifiers

PMID41390939
PMCPMC12701955

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.