Evidence mapPaperPMID 40928782Full record

Observational studyJAMA network open2025

Concomitant Comedications and Survival With First-Line Pembrolizumab in Advanced Non-Small-Cell Lung Cancer.

Adrien Rousseau, Noémie Simon-Tillaux, Stefan Michiels, Lisa Derosa, Ariane Laparra, David Planchard, Jordi Remon, Fabrice Barlesi, Pernelle Lavaud, Maxime Frelaut and 4 more

Abstract readObservational Study
In one paragraph

Observational study in JAMA network open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
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

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Adrien RousseauDepartment of Cancer Medicine, Gustave Roussy, Thoracic Group and International Center for Thoracic Cancers, Paris-Saclay University, Villejuif, France.
Noémie Simon-TillauxOncostat U1018, Institut National de la Santé et de la Recherche Médicale (INSERM), Ligue Contre le Cancer, Paris-Saclay University, Villejuif, France.
Stefan MichielsOncostat U1018, Institut National de la Santé et de la Recherche Médicale (INSERM), Ligue Contre le Cancer, Paris-Saclay University, Villejuif, France.
Lisa DerosaDepartment of Cancer Medicine, Gustave Roussy, Thoracic Group and International Center for Thoracic Cancers, Paris-Saclay University, Villejuif, France.
Ariane LaparraDepartment of Drug Development, Gustave Roussy, Paris-Saclay University, Villejuif, France.
David PlanchardDepartment of Cancer Medicine, Gustave Roussy, Thoracic Group and International Center for Thoracic Cancers, Paris-Saclay University, Villejuif, France.
Jordi RemonDepartment of Cancer Medicine, Gustave Roussy, Thoracic Group and International Center for Thoracic Cancers, Paris-Saclay University, Villejuif, France.
Fabrice BarlesiDepartment of Cancer Medicine, Gustave Roussy, Thoracic Group and International Center for Thoracic Cancers, Paris-Saclay University, Villejuif, France.
Pernelle LavaudDepartment of Cancer Medicine, Gustave Roussy, Thoracic Group and International Center for Thoracic Cancers, Paris-Saclay University, Villejuif, France.
Maxime FrelautDepartment of Cancer Medicine, Gustave Roussy, Thoracic Group and International Center for Thoracic Cancers, Paris-Saclay University, Villejuif, France.
Claudia ParisiDepartment of Cancer Medicine, Gustave Roussy, Thoracic Group and International Center for Thoracic Cancers, Paris-Saclay University, Villejuif, France.
Anas GazzahDepartment of Drug Development, Gustave Roussy, Paris-Saclay University, Villejuif, France.
Benjamin BesseDepartment of Cancer Medicine, Gustave Roussy, Thoracic Group and International Center for Thoracic Cancers, Paris-Saclay University, Villejuif, France.
Stéphanie FoulonOncostat U1018, Institut National de la Santé et de la Recherche Médicale (INSERM), Ligue Contre le Cancer, Paris-Saclay University, Villejuif, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Importance: Antibiotics, steroids, and proton pump inhibitors (PPIs) are suspected to decrease the efficacy of immunotherapy. Objective: To explore the association of comedications with overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC). Design, Setting, and Participants: This nationwide retrospective cohort study used target trial emulations of patients newly diagnosed with NSCLC from January 2015 to December 2022, identified from the French national health care database. Eligible patients were treated with pembrolizumab in a first-line setting and alive 2 months after initiating pembrolizumab. Exclusion criteria included hospitalization for infectious disease, autoimmune disorders, or peptic ulcer disease. Exposures: Antibiotic and PPI exposures were defined as at least 2 prescriptions 60 days before to 42 days after pembrolizumab start. Steroid exposure was defined as at least 2 prescriptions 30 days before to 30 days after pembrolizumab start. Main Outcomes and Measures: The primary outcome was OS. Patients exposed were compared with those without exposure, using inverse probability of treatment weighting (IPTW) to adjust for confounding. Results: Between January 2015, and December 2022, 41 529 patients were treated with first line pembrolizumab for advanced disease (27 826 male [67.0%]; median [range] age, 65 [19-97] years; 14 835 [35.7%] treated with pembrolizumab alone; 26 694 [64.3%] treated with pembrolizumab plus chemotherapy). At treatment initiation, 12 898 (41.9%) patients were exposed to antibiotics, 18 210 (59.1%) to steroids, and 16 783 (53.7%) to PPIs. After IPTW, antibiotics (except for macrolide and penicillin) were associated with shorter OS (hazard ratio [HR], 1.08; 95% CI, 1.05-1.12; P < .001), but it varied by antibiotic type. Steroids were not associated with OS (HR, 0.98; 95% CI, 0.95-1.02; P = .37); however, there was an interaction with pembrolizumab regimen (ie, pembrolizumab alone or with chemotherapy) (P for interaction < .001), and there was a dose-dependent association according to daily prednisone-equivalent dose (P for trend < .001). Steroids were associated with worse OS when prescribed at doses greater than 20 mg per day for pembrolizumab alone (P for trend = .005) and greater than 30 mg per day for pembrolizumab combined with chemotherapy (P for trend < .001). PPIs were associated with worse OS (HR, 1.13; 95% CI, 1.10-1.17; P < 001). Conclusions and Relevance: In this cohort study of patients with advanced NSCLC treated with pembrolizumab, exposure to some classes of antibiotics, to steroids (>20 mg per day of prednisone equivalent), and to PPIs was associated with worse OS, indicating that comedications should be monitored carefully in patients with immunotherapy.

Indexed as

Anti-Bacterial AgentsAntibodies, Monoclonal, HumanizedCarcinoma, Non-Small-Cell LungGlucocorticoidsImmune Checkpoint InhibitorsLung NeoplasmsProton Pump InhibitorsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsDrug InteractionsFemaleFranceHumansKaplan-Meier EstimateAnti-Bacterial AgentsAntibodies, Monoclonal, HumanizedGlucocorticoidsImmune Checkpoint InhibitorspembrolizumabProton Pump Inhibitors

Identifiers

PMID40928782
PMCPMC12423871

What Socratic holds

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Registered trials

None linked

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.