1063P - Influence of infusion timing on the outcomes of immunotherapy in a multi-tumor cohort

Background

Circadian modulation of inflammation-related genes has been involved in oscillations of T cell recruitment and effector functions during the daytime. Previous studies have suggested an influence of immune checkpoint inhibitors (ICI) infusion timing on treatment efficacy, although this effect has not been analyzed in large multi-tumor cohorts.

Methods

Retrospective study of patients with advanced solid tumors treated with ICI in a tertiary hospital (2015-2022). For each patient, the hour of each infusion during the first 3 months of ICI was collected from the treatment ward registry. Patients who received ≥75% of infusions before or after 4.30 pm were respectively classified into ‘AM’ or ‘PM’ groups. The same process was reproduced with 2.30 pm as cut-off. Data from each group were collected to calculate the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

Results

418 patients were evaluated (median age: 68.2). The most frequent tumor subtypes were NSCLC (31.6%), HNSCC (20.6%), urothelial (16%), renal (12.9%), and melanoma (12.2%). 64.1% received anti-PD1, 19.6% anti-PDL1, 14.1% anti-PD1 plus anti-CTLA4, and 2.2% anti-CTLA4 monotherapy (86% in 1^st/2^nd line, 14% in further lines). ECOG PS prior to C1 was 0-1 in 87.8%. 231 patients (55.3%) were classified as ‘AM’ and 56 (13.4%) as ‘PM’ with the 4.30 pm cut-off. With the 2.30 pm cut-off, 118 (28.2%) were ‘AM’ and 142 (34%) were ‘PM’. All the groups had balanced baseline characteristics. With the 4.30 pm cut-off, the ’PM’ group had significantly lower ORR (22.6% vs. 37.7%; p<0.01) and DCR (24.5% vs. 52%; p<0.001), and shorter PFS (3.1 vs. 4.8 m; p<0.05) and OS (5.6 vs. 14.8 m; p<0.05). Similar results were obtained with the 2.30 pm cut-off, observing lower ORR (24.8% vs. 37.7%; p<0.01), DCR (33.6% vs. 50%; p<0.01), and a tendency for shorter PFS (3.2 vs. 4.9 m; p=0.074) and OS (8.1 vs. 13.2 m; p<0.19). A lower DCR was observed in the ‘PM’ group for each tumor subtype in the subgroup analysis.

Conclusions

Our results confirm the effect of infusion timing on ICI outcomes in a large multi-tumor cohort, with lower response rates and worse survival outcomes in the ‘PM’ group patients. Prospective validation of these results would be of great clinical value.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P. Garrido Lopez: Financial Interests, Institutional, Advisory Board: Janssen, MSD, Novartis, Medscape, Takeda, AbbVie, Amgen, AstraZeneca, Bayer, BMS, Boehringer, Daiichi Sankyo, Lilly, Roche, Sanofi. A. Cortes Salgado: Financial Interests, Institutional, Advisory Board: AstraZeneca, PharmaMar, Daiichi Sankyo, MSD, Eisai, Accord Healthcare. P. Gajate: Financial Interests, Institutional, Advisory Board: BMS, Roche, Pfizer, Ipsen, MSD, Merck, Janssen, Astellas, Eisai, Novartis. All other authors have declared no conflicts of interest.