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

Landré, T.; Karaboué, A.; Buchwald, Z.S.; Innominato, P.F.; Qian, D.C.; Assié, J.B.; Chouaïd, C.; Lévi, F.; Duchemann, B.

doi:10.1016/j.esmoop.2023.102220

Cited by 16 publications

(3 citation statements)

References 52 publications

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“…On the basis of previous research, a threshold of infusions greater than or equal to 20% versus less than 20% received after the 3- PM cutoff time (the onset of durvalumab infusion) was adopted for the analysis. 6 , 7 , 8 Although most previous studies used 4:30 PM as the cutoff time ( Supplementary Table 1 ), 10 none of the patients in our cohort met this criterion because of the clinic's closing time. Consequently, we adjusted the cutoff time to 3 PM .…”

Section: Methodsmentioning

confidence: 95%

“… 6 Similar studies in metastatic NSCLC and pantumor meta-analysis also found that patients receiving late time-of-day infusions had significantly shorter progression-free survival (PFS) than those receiving early time-of-day infusions. 10 , 7 , 8 , 9 However, the association between the time of day of ICI infusions and clinical outcomes in patients with locally advanced NSCLC remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Brief Report: Clinical Outcomes by Infusion Timing of Immune Checkpoint Inhibitors in Patients With Locally Advanced NSCLC

Hirata,

Uehara,

Hakozaki

et al. 2024

JTO Clinical and Research Reports

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Section: Methodsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Brief Report: Clinical Outcomes by Infusion Timing of Immune Checkpoint Inhibitors in Patients With Locally Advanced NSCLC

Hirata,

Uehara,

Hakozaki

et al. 2024

JTO Clinical and Research Reports

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“…Noon was chosen as the time-of-day threshold of interest as it is the nearest hour to the median infusion time among all patients and aligns with precedence set by previous circadian rhythm studies of ICIs for melanoma and lung cancer, as well as vaccination for infectious disease. [20][21][22][23] The proportion threshold of 20% was set to optimize the balance between comparison group sample sizes (table 1).…”

Section: Open Accessmentioning

confidence: 99%

Impact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis

Patel,

Woo,

Draper

et al. 2024

J Immunother Cancer

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BackgroundRecent studies have demonstrated that earlier time-of-day infusion of immune checkpoint inhibitors (ICIs) is associated with longer progression-free survival (PFS) and overall survival (OS) among patients with metastatic melanoma and non-small cell lung cancer. These data are in line with growing preclinical evidence that the adaptive immune response may be more effectively stimulated earlier in the day. We sought to determine the impact of time-of-day ICI infusions on outcomes among patients with metastatic renal cell carcinoma (mRCC).MethodsThe treatment records of all patients with stage IV RCC who began ICI therapy within a multicenter academic hospital system between 2015 and 2020 were reviewed. The associations between the proportion of ICI infusions administered prior to noon (denoting morning infusions) and PFS and OS were evaluated using univariate and multivariable Cox proportional hazards regression.ResultsIn this study, 201 patients with mRCC (28% women) received ICIs and were followed over a median of 18 months (IQR 5–30). The median age at the time of ICI initiation was 63 years (IQR 56–70). 101 patients (50%) received ≥20% of their ICI infusions prior to noon (Group A) and 100 patients (50%) received <20% of infusions prior to noon (Group B). Across the two comparison groups, initial ICI agents consisted of nivolumab (58%), nivolumab plus ipilimumab (34%), and pembrolizumab (8%). On univariate analysis, patients in Group A had longer PFS and OS compared with those in Group B (PFS HR 0.67, 95% CI 0.48 to 0.94, Punivar=0.020; OS HR 0.57, 95% CI 0.34 to 0.95, Punivar=0.033). These significant findings persisted following multivariable adjustment for age, sex, performance status, International Metastatic RCC Database Consortium risk score, pretreatment lactate dehydrogenase, histology, and presence of bone, brain, and liver metastases (PFS HR 0.70, 95% CI 0.50 to 0.98, Pmultivar=0.040; OS HR 0.57, 95% CI 0.33 to 0.98, Pmultivar=0.043).ConclusionsPatients with mRCC may benefit from earlier time-of-day receipt of ICIs. Our findings are consistent with established mechanisms of chrono-immunology, as well as with preceding analogous studies in melanoma and lung cancer. Additional prospective randomized trials are warranted.

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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

Janopaul‐Naylor,

Boe,

et al. 2024

Head & Neck

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BackgroundPrior work documented circadian rhythm impacts on efficacy and toxicity of cancer therapies.MethodsSecondary 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).ResultsOf 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.ConclusionsFurther work may elucidate circadian impacts on select patients, tumors, and therapies; however, we found no significant effect in this study.

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

Cited by 16 publications

References 52 publications

Brief Report: Clinical Outcomes by Infusion Timing of Immune Checkpoint Inhibitors in Patients With Locally Advanced NSCLC

Brief Report: Clinical Outcomes by Infusion Timing of Immune Checkpoint Inhibitors in Patients With Locally Advanced NSCLC

Impact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis

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

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