Evidence map›Paper›PMID 36405729›Full record

ArticleFrontiers in immunology2022

Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab.

Agnish Dey, Matthew Austin, Harriet M Kluger, Nataliya Trunova, Helen Mann, Norah Shire, Claire Morgan, Diansong Zhou, Ganesh M Mugundu

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 27% of its field
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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Trial
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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

9 authors at 4 institutions in 2 countries.

Agnish DeyClinical Pharmacology and Quantitative Pharmacology, Biopharmaceuticals R&D, AstraZeneca, Boston, MA, United States.
Matthew AustinSchool of Medicine, Yale University, New Haven, CT, United States.
Harriet M KlugerSchool of Medicine, Yale University, New Haven, CT, United States.
Nataliya TrunovaImmuno-Oncology Franchise, Oncology R&D, AstraZeneca, Gaithersburg, MD, United States.
Helen MannOncology Biometrics, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
Norah ShireLate Development Oncology, Oncology R&D, AstraZeneca, Gaithersburg, MD, United States.
Claire MorganPatient Safety Oncology, AstraZeneca, Gaithersburg, MD, United States.
Diansong ZhouClinical Pharmacology and Quantitative Pharmacology, Biopharmaceuticals R&D, AstraZeneca, Boston, MA, United States.
Ganesh M MugunduClinical Pharmacology and Quantitative Pharmacology, Biopharmaceuticals R&D, AstraZeneca, Boston, MA, United States.
AstraZeneca (United States) · USYale University · USAstraZeneca (United Kingdom) · GBNational Patient Safety Foundation · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Immune-mediated adverse events (imAEs) may be associated with response to immune checkpoint inhibitors. We assessed the relationship between imAE development and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab (anti-programmed cell death ligand-1 [PD-L1]) alone or in combination with tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4). Methods: The analysis used individual patient-level data from 307 and 310 patients in the monotherapy and combination arms of MYSTIC, respectively. We evaluated the association between treatment efficacy and development of imAEs using univariate and multivariate survival analyses. Using machine learning, we built a predictive model utilizing baseline clinical and laboratory features to identify patients at risk of developing imAEs and further evaluated patient survival based on a threshold index extracted from the model. Results: Patients who developed any grade of imAE had improved overall survival versus patients without (hazard ratio [HR] 0.51; 95% confidence interval [CI]: 0.41-0.62). imAE development was associated with improved overall survival (HR 0.54; 95% CI 0.44-0.66) in a multivariate Cox proportional hazard model considering patient demographic features and baseline characteristics. Higher odds of imAE development were observed (odds ratio 3.023; 95% CI: 1.56-5.83) in responders versus non-responders in patients treated with immunotherapy. Based on baseline characteristics, the random forest classification algorithm was used to formulate a predictive model to identify patients at increased risk of developing imAEs during treatment. Conclusion:

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedHumansAntibodies, MonoclonalAntibodies, Monoclonal, Humanizeddurvalumabtremelimumabbiomarkersbiostatisticsclinical trialscomputational methodsimmunologyimmunotherapylung cancermethodology and modeling

Identifiers

PMID36405729
PMCPMC9670978
OpenAlexW4308098925

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.