Evidence map›Paper›PMID 42134900›Full record

Trial reportJournal for immunotherapy of cancer2026

Morning versus afternoon administration of immune checkpoint inhibitors in metastatic non-small-cell lung cancer.

Rachel T Gonzalez, Reena Datta, Sadiq Rehmani, Garth W Strohbehn, Nithya Ramnath, Shadia Jalal, Michael P Dykstra, Josiah Nieto, David Elliott, Matthew J Schipper and 1 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal for immunotherapy of cancer, 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

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

11 authors.

Rachel T GonzalezDepartment of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
Reena DattaDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.
Sadiq RehmaniDivision of Hematology/Oncology, University of Michigan, Ann Arbor, Michigan, USA.
Garth W StrohbehnSection of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Nithya RamnathDivision of Hematology/Oncology, University of Michigan, Ann Arbor, Michigan, USA.
Shadia JalalDepartment of Internal Medicine, Indiana University Melvin, Indianapolis, Indiana, USA.
Michael P DykstraDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.
Josiah NietoDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.ORCID http://orcid.org/0009-0002-3930-0708
David ElliottDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.
Matthew J SchipperDepartment of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
Alex K BryantDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA alex.bryant@va.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCircadian biology suggests that synchronizing immune checkpoint inhibitor (ICI) dosing with morning peaks in immune activation could improve clinical outcomes, but well-powered studies using appropriate causal inference methodology are sparse.

methodsWe emulated a pragmatic randomized controlled trial of AM versus PM ICI infusions using Veterans Health Administration records from 2010 to 2024. In the emulated trial, stage IV non-small-cell lung cancer patients planned to undergo first-line or second-line ICI would have been randomized to receive the first three infusions in the AM (<12:00 PM) or PM (≥12:00 PM). The primary outcome was overall survival (OS). Marginal structural models with inverse probability of censoring weights estimated the per-protocol effect, accounting for baseline and longitudinal confounding. A historical chemotherapy cohort served as a negative control.

results4688 patients were eligible for the emulated trial; of these, 1171 received their first three infusions in the AM and 794 in the PM. Median follow-up was 4.7 years. Median survival was 10.3 months (AM) vs 8.1 months (PM). PM dosing was associated with worse OS (HR for PM versus AM 1.15, 95% CI 1.04 to 1.26, p=0.004). In 7951 chemotherapy controls (median follow-up 8.9 years), no time-of-day effect was detected (HR for PM vs AM 1.05, 95% CI 0.98 to 1.12, p=0.15). Results were robust in sensitivity analyses.

conclusionsMorning ICI infusions confer a modest but clinically meaningful survival benefit that is absent in chemotherapy controls, supporting a causal chronotherapeutic effect. Scheduling ICIs before noon represents a low-cost, immediately actionable strategy warranting prospective confirmation.

Indexed as

Carcinoma, Non-Small-Cell LungImmune Checkpoint InhibitorsLung NeoplasmsAgedDrug Administration ScheduleFemaleHumansMaleMiddle AgedNeoplasm MetastasisImmune Checkpoint InhibitorsImmunotherapyLung Cancer

Identifiers

PMID42134900
PMCPMC13182366

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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.