Evidence map›Paper›PMID 36049656›Full record

SynthesisJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2022

Cox Proportional Hazard Ratios Overestimate Survival Benefit of Immune Checkpoint Inhibitors: Cox-TEL Adjustment and Meta-Analyses of Programmed Death-Ligand 1 Expression and Immune Checkpoint Inhibitor Survival Benefit.

Emily Pei-Ying Lin, Chih-Yuan Hsu, Jeng-Fong Chiou, Lynne Berry, Leora Horn, Paul Bunn, James Chih-Hsin Yang, Pan-Chyr Yang, Alex A Adjei, Yu Shyr

Open access · greenAbstract readMeta-Analysis
In one paragraph

Synthesis in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2022. 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
0.1field-weighted citation impact, top 53% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. 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

10 authors at 6 institutions in 2 countries.

Emily Pei-Ying LinDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Department of Medical Research, Taipei Medical University Hospital, Taipei, Taiwan.
Chih-Yuan HsuDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
Jeng-Fong ChiouDepartment of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan; Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Lynne BerryDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
Leora HornDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Paul BunnDepartment of Medicine, University of Colorado School of Medicine, Aurora, Colorado.
James Chih-Hsin YangDepartment of Oncology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
Pan-Chyr YangDepartment of Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Alex A AdjeiTaussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
Yu ShyrDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan. Electronic address: yu.shyr@vumc.org.
Vanderbilt University Medical Center · USTaipei Medical University Hospital · TWCleveland Clinic · USInstitute of Biomedical Sciences, Academia Sinica · TWNational Taiwan University Hospital · TWUniversity of Colorado Denver · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8M
TISSUE CoreP50CA098131 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PARK, BEN HO, PIETENPOL, JENNIFER A · 2003 to 2024
$48.7M
TrainingU54CA163072 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Tuya Pal, Karen Marie Winkfield · 2011 to 2026
$20.1M
Vanderbilt-Ingram Cancer Center SPORE in Gastrointestinal CancerP50CA236733 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Robert J. Coffey · 2019 to 2026
$19.6M
Coordinating center for the NCI small cell lung cancer research consortiumU24CA213274 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Lauren Averett Byers, JOHN D. MINNA · 2017 to 2026
$12.9M
Barrett's Esophagus Translational Research Network Coordinating Center (BETRNetCC)U24CA163056 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SHYR, YU · 2017 to 2022
$2.1M
NCI NIH HHS P30 CA068485NCI NIH HHS P50 CA098131NCI NIH HHS P50 CA236733NCI NIH HHS U24 CA163056NCI NIH HHS U24 CA213274NCI NIH HHS U54 CA163072
6 · The paper itself

Abstract

introductionSurvival benefit of immune checkpoint inhibitor (ICI) therapy in lung cancer is not fully understood.

methodsPubMed-cataloged publications through February 14, 2022, were queried for randomized controlled trials of ICI in lung cancer, and identified publications were reviewed for inclusion. Reported Cox hazard ratios (HRs) for overall survival were transformed to Cox-TEL HR for ICI short-term survivors (ST-HR) and difference in proportions for patients with long-term survival (LT-DP). Meta-analyses were performed using a frequentist random-effect model. Outcomes of interest were pooled overall survival Cox HR, ST-HR, and LT-DP in NSCLC, stratified by programmed death-ligand 1 (PD-L1) level (primary outcome) and ICI treatment line (secondary).

resultsA total of nine publications representing eight clinical trials were selected for meta-analysis. Primary analysis yielded the following metrics for patients with PD-L1 expression less than 1%, more than or equal to 1%, and more than or equal to 50%, respectively: pooled Cox HR, 0.71 (95% confidence interval [CI]: 0.62-0.82), 0.74 (95% CI: 0.68-0.82), and 0.62 (95% CI: 0.54-0.70); pooled ST-HR, 0.91 (95% CI: 0.79-1.05), 0.88 (95% CI: 0.82-0.94), and 0.70 (95% CI: 0.60-0.83); and pooled LT-DP, 0.10 (95% CI: 0.00-0.20), 0.09 (95% CI: 0.06-0.12), and 0.11 (95% CI: 0.05-0.17). Results of secondary analysis revealed LT-DP of approximately 10% across treatment lines.

conclusionsThis study reveals an approximately 10% long-term survival probability increment in ICI long-term survivors across PD-L1-positive subpopulations in both ICI treatment lines. Furthermore, ST-HR was consistently poorer than Cox HR. For patients with PD-L1 less than 1%, neither LT-DP nor ST-HR achieved statistical significance. The analysis provides greater insight into the treatment effect of ICI in published trials.

Indexed as

B7-H1 AntigenLung NeoplasmsHumansImmune Checkpoint InhibitorsProgrammed Cell Death 1 ReceptorB7-H1 AntigenCD274 protein, humanImmune Checkpoint InhibitorsProgrammed Cell Death 1 ReceptorCox HRCox-TELImmune checkpoint inhibitorLong-term survivalPD-L1

Identifiers

PMID36049656
PMCPMC9948805
OpenAlexW4293522042

What OpenQuestion 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 OpenQuestion graph.