Evidence mapPaperPMID 41501995Full record

ArticleJNCI cancer spectrum2026

Heterogeneous treatment effect of immune checkpoint inhibitors by pretreatment prognosis in randomized controlled trials.

Lee X Li, Adel Shahnam, Ganessan Kichenadasse, Lewis Murray, Richard Woodman, Ahmad Y Abuhelwa, Natansh D Modi, Andrew Rowland, Ashley M Hopkins, Michael J Sorich

Abstract read
In one paragraph

Article in JNCI cancer spectrum, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Lee X LiCollege of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia.ORCID 0000-0001-5259-5198
Adel ShahnamDepartment of Medical Oncology, Peter McCallum Cancer Centre, Melbourne, Australia.ORCID 0000-0002-0043-8374
Ganessan KichenadasseCollege of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia.ORCID 0000-0001-9923-5149
Lewis MurrayDepartment of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia.ORCID 0000-0003-0562-4747
Richard WoodmanCollege of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia.ORCID 0000-0002-4094-1222
Ahmad Y AbuhelwaDepartment of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates.ORCID 0000-0002-4182-065X
Natansh D ModiClinical and Health Sciences, University of South Australia, Adelaide, Australia.ORCID 0000-0003-3262-5374
Andrew RowlandCollege of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia.ORCID 0000-0002-8946-3954
Ashley M HopkinsCollege of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia.ORCID 0000-0001-7652-4378
Michael J SorichCollege of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia.ORCID 0000-0003-1999-866X

Funding

Beat Cancer Research Fellowship from the Cancer Council South AustraliaNational Health and Medical Research Council APP2008119National Health and Medical Research Council GNT2013565University of Sharjah Targeted Research 2301110392
6 · The paper itself

Abstract

backgroundTreatment response to immune checkpoint inhibitors varies considerably, a phenomenon known as heterogeneity of treatment effect. Heterogeneity of treatment effect is explored via one-variable-at-a-time subgroup analyses in randomized controlled trials (RCTs), however, this method has limitations, which the risk-modeling approach seeks to address.

methodsApplying the risk-modeling approach, individual patient data from 10 RCTs (6 supporting US Food and Drug Administration's atezolizumab label: OAK, IMpower130, IMpower150, IMpower133, IMbrave150, IMspire150; 4 unlabeled indications: IMpower131, IMpower132, IMmotion151, and IMvigor211) were analyzed by an extreme gradient-boosting algorithm to predict pretreatment prognosis for overall survival. The predicted risk scores were evaluated as efficacy modifiers categorically (high-, intermediate-, low-risk groups) and continuously in Cox models with treatment-by-risk-group interaction terms. Sensitivity and exploratory analyses investigated absolute and meta-analyzed treatment effect and compared the results with established prognostic tools and treatment effect predictors. Statistical significance tests are 2-sided.

resultsAmong the 10 RCTs (n = 7053), one trial (IMvigor211) showed statistically significant heterogeneity of treatment effect by pretreatment prognosis across all evaluations (risk groups, risk scores, sensitivity analyses: P < .001). Among other trials, no statistically significant heterogeneity of treatment effect was detected (risk group and risk score analysis interaction test: OAK P = .61 and P = .77; IMpower130 P = .13 and P = .52; IMpower131 P = .21 and P = .02; IMpower150 P = .14 and P = .36; IMpower133 P = .38 and P = .12; IMbrave150 P = .15 and P = .08; IMspire150 P = .24 and P = .6; IMpower132 P = .15 and P = .81; IMmotion151 P = .48 and P = .21, respectively).

conclusionsThe risk-modeling approach showed no clear link between pretreatment prognosis and immune checkpoint inhibitor efficacy in most RCTs, particularly those supporting atezolizumab's Food and Drug Administration label. In IMvigor211, patients with better pretreatment prognosis were more likely to benefit from atezolizumab treatment for platinum-refractory metastatic urothelial carcinoma.

Indexed as

Immune Checkpoint InhibitorsNeoplasmsRandomized Controlled Trials as TopicTreatment Effect HeterogeneityAntibodies, Monoclonal, HumanizedHumansPrognosisProportional Hazards ModelsAntibodies, Monoclonal, HumanizedatezolizumabImmune Checkpoint Inhibitors

Identifiers

PMID41501995
PMCPMC13126119

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.