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Clinical Trial
. 2024 Sep;46(9):2292-2300.
doi: 10.1002/hed.27825. Epub 2024 May 24.

Effect of time-of-day nivolumab and stereotactic body radiotherapy in metastatic head and neck squamous cell carcinoma: A secondary analysis of a prospective randomized trial

James R Janopaul-Naylor  1 , Lillian Boe  2 , Yao Yu  1 , Eric J Sherman  3   4 , David G Pfister  3   4 , Nancy Y Lee  1 , Sean McBride  1
Affiliations
Clinical Trial

Effect of time-of-day nivolumab and stereotactic body radiotherapy in metastatic head and neck squamous cell carcinoma: A secondary analysis of a prospective randomized trial

James R Janopaul-Naylor et al. Head Neck. 2024 Sep.

Abstract

Background: Prior work documented circadian rhythm impacts on efficacy and toxicity of cancer therapies.

Methods: Secondary analysis of prospective, phase II trial of metastatic HNSCC randomized to nivolumab+/-SBRT. Used cutoffs of 1100 and 1630. Timing classified by first infusion or majority of SBRT (e.g., PM SBRT defined by two or three fractions after 1630).

Results: Of 62 patients, there was no significant difference in median PFS between AM nivolumab (n = 7, 175 days), PM nivolumab (n = 21, 58 days), or Mid-Day nivolumab (n = 34, 67 days; p = 0.8). There was no significant difference in median PFS with AM SBRT (n = 4, 78 days), PM SBRT (n = 13, 111 days), or Mid-Day SBRT (n = 15, 63 days; p = 0.8). There was no significant difference in Grade 3-4 toxicity or ORR. Sensitivity analyses with other timepoints were negative.

Conclusions: Further work may elucidate circadian impacts on select patients, tumors, and therapies; however, we found no significant effect in this study.

Keywords: chrono‐oncology; circadian rhythm; head and neck cancer; immunotherapy; stereotactic body radiotherapy.

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Figures

Figure 1:
Figure 1:
Kaplan-Meier plots of Overall Survival (A) and Progression Free Survival (B) over time (days) based on time of first nivolumab infusion.
Figure 2:
Figure 2:
Kaplan-Meier plots of Overall Survival (A) and Progression Free Survival (B) over time (days) based on proportion of all nivolumab infusions delivered after 4:30 PM (< 20% compared to ≥ 20%).
Figure 3:
Figure 3:
Kaplan-Meier plots of Overall Survival (A) and Progression Free Survival (B) over time (days) based on timing of majority of radiotherapy treatments. Mid-Day RT defined as patients not having majority of radiotherapy treatments either before 11:00 AM or after 4:30 PM.
See this image and copyright information in PMC

References

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