Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers - a study-level meta-analysis

Q: What question does this meta-analysis address?

It assesses whether the time of day when ICIs are infused affects overall survival and progression-free survival in patients with advanced cancers.

Q: How were studies selected and data pooled?

Studies were required to use a defined ToD cut-off, and hazard ratios for early versus late ToD were collected and pooled across reports.

Q: What did the pooled results show about early vs late infusion time?

Across 13 studies, early ToD infusion groups had longer OS and PFS than late ToD groups, with statistically significant pooled hazard ratios.

Q: What is the clinical implication and next research step?

Selected metastatic cancer patients may benefit from early ToD ICI infusions, but prospective randomized trials are needed to establish optimal circadian timing recommendations.

Sep 21, 2026

Uploaded by Finn

This study-level meta-analysis evaluates whether the time of day (ToD) of immune checkpoint inhibitor (ICI) infusion influences outcomes in advanced cancers. Progression-free survival (PFS) and overall survival (OS) hazard ratios from studies using a defined ToD cut-off were pooled. Thirteen studies involving 1663 patients showed early ToD ICI infusions were associated with longer OS and PFS versus late ToD. Findings support circadian mechanisms and indicate a need for prospective randomized trials.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Background

Materials and methods

Results

Conclusions

Introduction

Circadian rhythms and cancer

ORIGINAL RESEARCH Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis T. Landré1, A. Karaboué2 , 3, Z. S. Buchwald4, P. F. Innominato5, 6, D. C. Qian4, J. B. Assié7, 8, C. Chouaïd7, 8, F. Lévi3, 6, 9 & B. Duchemann10􀀁 1Hôpitaux Universitaires Paris Saint-Denis, UCOG, Assistance Publique - Hôpitaux de Paris, Sevran; 2Medical Oncology Unit, GHT Paris Grand Nord-Est, Le RaincyMontfermeil, Montfermeil; 3UPR ‘Chronotherapy, Cancer and Transplantation’, Paris-Saclay University Medical School, Villejuif, France; 4Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, USA; 5Oncology Department, Ysbyty Gwynedd, Betsi Cadwaladr University Health Board, Bangor; 6Cancer Research Centre, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK; 7Pneumology Service, CHI Créteil, Créteil; 8Inserm U955, UPEC, IMRB, Créteil; 9Gastro-intestinal and Medical Oncology Service, Paul-Brousse Hospital, Assistance Publique - Hôpitaux de Paris, Villejuif; 10Thoracic and Medical Oncology Unit, Avicenne Hospital, Assistance Publique - Hôpitaux de Paris, Bobigny, France Available online 16 January 2024 Background: Immune checkpoint inhibitors (ICIs) have become the standard of care for numerous malignancies. Emerging evidence suggests that the time of day (ToD) of ICI administration could impact the outcomes of patients with cancer. The consistency of ToD effects on ICI efﬁcacy awaits initial evaluation. Materials and methods: This meta-analysis integrates progression-free survival (PFS) and overall survival (OS) data from studies with a deﬁned ‘cut-off’ ToD. Hazard ratios (HRs) [95% conﬁdence interval (CI)] of an earlier progression or death according to ‘early’ or ‘late’ ToD of ICIs were collected from each report and pooled. Results: Thirteen studies involved 1663 patients (Eastern Cooperative Oncology Group performance status 0-1, 83%; males/females, 67%/33%) with non-small-cell lung cancer (47%), renal cell carcinoma (24%), melanoma (20%), urothelial cancer (5%), or esophageal carcinoma (4%) . Most patients received anti-programmed cell death protein 1 or anti-programmed death-ligand 1 (98%), and a small proportion also received anti-cytotoxic T-lymphocyteassociated protein 4 (anti-CTLA-4) (18%) . ToD cut-offs were 13:00 or 14:00 (i.e. ICI median infusion time), for six studies, and 16:00 or 16:30 (i.e. reported threshold for weaker vaccination responses) for seven studies. Pooled analyses revealed that the early ToD groups had longer OS (HR 0 .50, 95% CI 0 .42-0.58; P < 0.00001) and PFS (HR 0.51, 95% CI 0 .42-0.61; P < 0.00001) compared with the late ToD groups. Conclusions: Patients with selected metastatic cancers seemed to largely beneﬁt from early ToD ICI infusions, which is consistent with circadian mechanisms in immune-cell functions and trafﬁcking. Prospective randomized trials are needed to establish recommendations for optimal circadian timing of ICI-based cancer therapies. Key words: immunotherapy, chronotherapy, immune checkpoint inhibitors, meta-analysis, circadian rhythms INTRODUCTION The time of day (ToD) of administration has not been speciﬁed nor evaluated in clinical trials assessing the efﬁcacy and adverse events of checkpoint inhibitors (ICIs), but is anticipated to have occurred mostly in the morning.1,2 However,ﬁndings in several retrospective clinical studies have indicated that ICI infusion ToD is usually spread between 08:00 and 18:00, and could affect treatment efﬁcacy. Such results are in line with those from prior randomized chronotherapy *Correspondence to: Dr Boris Duchemann, Hôpital Avicenne (AP-HP), 125, rue de Stalingrad, 93000 Bobigny, France. Tel: þ33-01-48-95-55-55; Fax: þ33-01- 41-52-55-66 E-mail: [boris.duchemann@aphp.fr](boris.duchemann@aphp.fr) (B. Duchemann). 2059-7029/© 2023 The Author(s). Published by Elsevier Ltd on behalf of European Society

FAQs

What question does this meta-analysis address?

It assesses whether the time of day when ICIs are infused affects overall survival and progression-free survival in patients with advanced cancers.

How were studies selected and data pooled?

Studies were required to use a defined ToD cut-off, and hazard ratios for early versus late ToD were collected and pooled across reports.

What did the pooled results show about early vs late infusion time?

Across 13 studies, early ToD infusion groups had longer OS and PFS than late ToD groups, with statistically significant pooled hazard ratios.

What is the clinical implication and next research step?

Selected metastatic cancer patients may benefit from early ToD ICI infusions, but prospective randomized trials are needed to establish optimal circadian timing recommendations.

Sep 21, 2026

Uploaded by Finn