Association Between Time-of-Day of Immune Checkpoint Blockade Administration and Outcomes in Metastatic Renal Cell Carcinoma

Early Morning Checkpoint Inhibitor Infusion and Overall Survival of Patients with Metastatic Cancer: an In-depth Chronotherapeutic Study

“…For patients with PS2-3, low timing impact might be explained by the dampening or loss of proper circadian organization 1,26 . Our results are in line with the eight recently published studies on cancer chrono-immunotherapies which investigated almost exclusively PS0-1 patients and all concluded on the best timing group being the earliest studied one, either in terms of OS, PFS or response, regardless of the chosen morning/afternoon timing cut-off 17–24 . Here, timing univariable effect was more pronounced in women than in men (Figure 1C, Figure S7).…”

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

“…The search found 16 studies, including 8 articles in peer-reviewed international journals 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 and 8 congress abstracts, which were presented as poster communications at major international congresses. 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 Three abstracts were discarded because the data 40 were updated in a subsequently published article, 26 or detailed HR data were not reported.…”

“… 34 , 35 All 13 retained study reports consisted of retrospective evaluations of ToD ICI administration effects. They involved patients receiving ICIs for metastatic lung cancer, 26 , 27 , 28 , 36 , 39 malignant melanoma, 25 , 30 , 32 urothelial cancer, 33 renal cell carcinoma, 29 , 37 , 38 and esophageal carcinoma. 31 ICIs were anti-PD-1 and/or anti-PD-L1, which were combined with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) ipilimumab for some patients in five studies 25 , 29 , 30 , 32 , 37 ( Supplementary Figure S1 , available at https://doi.org/10.1016/j.esmoop.2023.102220 ).…”

“…The percentage of infusions administered after this threshold that was associated with a weak efficacy of ICIs also differed from 20% to 75% between studies. Most studies considered all the immunotherapy cycles, 25 , 26 , 27 , 28 , 29 , 31 , 33 , 36 , 37 , 38 but a few studies only considered the initial ones. 30 , 31 , 39 …”

“…The ToD ‘cut-off’ was 16:00 for one study 36 and 16:30 for six others. 25 , 27 , 28 , 29 , 33 , 38 For those seven studies, the early ToD groups consisted of patients receiving fewer than 20% of their ICI infusions after the cut-off time. The patients in the late ToD groups received at least 20% of their ICI infusions after that cut-off time.…”