Evidence map›Paper›PMID 39083541›Full record

ArticlePloS one2024

Head-to-head comparison of composite and individual biomarkers to predict clinical benefit to PD-1 blockade in non-small cell lung cancer.

Karlijn Hummelink, Vincent van der Noort, Mirte Muller, Robert D Schouten, Michel M van den Heuvel, Daniela S Thommen, Egbert F Smit, Gerrit A Meijer, Kim Monkhorst

Abstract readComparative Study
In one paragraph

Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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. Article
  2. Review
  3. Review
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.

Karlijn HummelinkDepartment of Pathology, Division of Diagnostic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID 0000-0003-4371-8904
Vincent van der NoortDepartment of Biometrics, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID 0000-0002-4910-4535
Mirte MullerDepartment of Thoracic Oncology, Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Robert D SchoutenDepartment of Thoracic Oncology, Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID 0000-0002-7014-470X
Michel M van den HeuvelDepartment of Thoracic Oncology, Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID 0000-0002-6372-2153
Daniela S ThommenDivision of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID 0000-0002-7431-2854
Egbert F SmitDepartment of Thoracic Oncology, Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID 0000-0002-7329-6995
Gerrit A MeijerDepartment of Pathology, Division of Diagnostic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Kim MonkhorstDepartment of Pathology, Division of Diagnostic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe efficacy of PD-1 blocking agents in advanced NSCLC has shown prolonged effectiveness, but only in a minority of patients. Multiple biomarkers have been explored to predict treatment benefit, yet their combined performance remains inadequately examined. In this study, we assessed the combined predictive performance of multiple biomarkers in NSCLC patients treated with nivolumab.

methodsPretreatment samples from 135 patients receiving nivolumab were used to evaluate the predictive performance of CD8 tumor-infiltrating lymphocytes (TILs), intratumoral (IT) localization of CD8 TILs, PD-1 high expressing TILs (PD1T TILs), CD3 TILs, CD20 B-cells, tertiary lymphoid structures (TLS), PD-L1 tumor proportion score (TPS) and the Tumor Inflammation score (TIS). Patients were randomly assigned to a training (n = 55) and validation cohort (n = 80). The primary outcome measure was Disease Control at 6 months (DC 6m) and the secondary outcome measure was DC at 12 months (DC 12m).

resultsIn the validation cohort, the two best performing composite biomarkers (i.e. CD8+IT-CD8 and CD3+IT-CD8) demonstrated similar or lower sensitivity (64% and 83%) and NPV (76% and 85%) compared to individual biomarkers PD-1T TILs and TIS (sensitivity: 72% and 83%, NPV: 86% and 84%) for DC 6m, respectively. Additionally, at 12 months, both selected composite biomarkers (CD8+IT-CD8 and CD8+TIS) demonstrated inferior predictive performance compared to PD-1T TILs and TIS alone. PD-1T TILs and TIS showed high sensitivity (86% and 100%) and NPV (95% and 100%) for DC 12m. PD-1T TILs could more accurately discriminate patients with no long-term benefit, as specificity was substantially higher compared to TIS (74% versus 39%).

conclusionComposite biomarkers did not show improved predictive performance compared to PD-1T TILs and TIS alone for both the 6- and 12-month endpoints. PD-1T TILs and TIS identified patients with DC 12m with high sensitivity. Patients with no long-term benefit to PD-1 blockade were most accurately identified by PD-1T TILs.

Indexed as

Biomarkers, TumorCarcinoma, Non-Small-Cell LungLung NeoplasmsLymphocytes, Tumor-InfiltratingNivolumabProgrammed Cell Death 1 ReceptorAdultAgedCD8-Positive T-LymphocytesFemaleHumansImmune Checkpoint InhibitorsMaleMiddle AgedTreatment OutcomeBiomarkers, TumorImmune Checkpoint InhibitorsNivolumabPDCD1 protein, humanProgrammed Cell Death 1 Receptor

Identifiers

PMID39083541
PMCPMC11290656

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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 OpenQuestion graph.