Clinical outcomes by infusion timing of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer

Adrien Rousseau, Marco Tagliamento, Edouard Auclin, Mihaela Aldea, Maxime Frelaut, Antonin Levy, Jose C. Benitez, Charles Naltet, Pernelle Lavaud, Angela Botticella, Miruna Grecea, Nathalie Chaput, Fabrice Barlesi, David Planchard, Benjamin Besse

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    16 Citations (Scopus)

    Résumé

    Background: We aimed to determine whether immune checkpoint inhibitors (ICI) time-of-day infusion might influence the survival of patients with advanced non-small cell lung cancer (NSCLC). Methods: We retrospectively analysed patients who received single-agent anti-PD-(L)1 therapy in any line between 2016 and 2021. We calculated by Cox regression models the association between the proportion of ICI infusions received after 16:30h and overall survival (OS) and progression-free survival (PFS). Results: 180 patients were included, 77% received ICI as second- or further-line (median of 12 infusions/patient). The median age was 65 years (IQR 57–70), 112 patients (62%) were male, 165 (92%) were current or former tobacco smokers, 140 (78%) had performance status (PS) 0 or 1, 26 (14%) were on steroid therapy at ICI initiation. Histology was non-squamous for 139 (77%), the median number of metastatic sites was 3, and 33% had brain metastases. Patients who received at least 20% of ICI infusions after 16:30h (65 out of 180, 36%) had a statistically significant shorter median PFS as compared with patients receiving less than 20% of infusions in the evening (4.9 vs 9.4 months, log-rank p = 0.020), while numerical but not statistical shorter OS was observed (14.0 vs 26.2 months, log-rank p = 0.090). In the multivariate analysis, receiving at least 20% of evening infusions did not significantly increase the risk of death, while PS and line of treatment were significantly correlated with the OS. On the contrary, a proportion of ICI administration after 16:30h ≥20% conferred an HR for the PFS of 1.44 (95% CI: 1.01–2.05, p = 0.043), but this prognostic effect was not found when including in the model the total number of ICI infusions received (HR 1.20, 95% CI: 0.83–1.75, p = 0.329). Conclusion: Time-of-day infusion of ICI may impact the survival of patients with advanced NSCLC. Underlying prognostic characteristics and the number of infusions received could represent conceivable confounding factors, linked to increased variance related to ICI infusion timing. Nonetheless, further studies may unravel chronobiological mechanisms modulating ICI efficacy.

    langue originaleAnglais
    Pages (de - à)107-114
    Nombre de pages8
    journalEuropean Journal of Cancer
    Volume182
    Les DOIs
    étatPublié - 1 mars 2023

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