503P - Clinical outcomes by infusion timing of immune checkpoint inhibitors in patients with locally advanced NSCLC

Background

Circadian fluctuations in T-cell function may modulate the efficacy of immune checkpoint inhibitors (ICIs). An association between time-of-day of ICI infusion and outcomes in patients with advanced non-small cell lung cancer (NSCLC) and melanoma has been reported; however, such association in patients with locally advanced NSCLC remains unclear. We aimed to determine whether durvalumab time-of-day infusion could impact the survival of patients with locally advanced NSCLC.

Methods

We retrospectively analyzed patients with unresectable locally advanced NSCLC treated with chemoradiation and adjuvant durvalumab between January 2018 and May 2022. According to previous research, the receipt of ≥20% vs <20% of infusions after the 15:00h cut-off time was set as the threshold for analysis. We calculated the association between the proportion of durvalumab infusions after 15:00h and survival (PFS [progression-free survival] and OS [overall survival]) using Cox regression.

Results

82 patients were included. The median age was 69 years (IQR, 44–85), 67 patients (82%) were male, 78 (95%) were current or former tobacco smokers, and 79 (96%) had performance status (PS) 0 or 1. Histology was non-squamous for 49 (60%). PD-L1 expression <50% was for 36 (44%). Patients who received at least 20% of durvalumab infusions after 15:00h (12 out of 82, 15%) vs. less than 20% of durvalumab infusions (70 out of 82, 85%) had a statistically significant shorter PFS (median 6.4 months vs not reached, HR: 0.36 [95% CI: 0.16–0.80], P = 0.011) and a trend of shorter OS (median 20.4 months vs not reached, HR: 0.36 [95% CI: 0.21–1.23], P = 0.16). In the multivariate analysis, patients who received at least 20% of durvalumab infusions after 15:00h vs. less than 20% of durvalumab infusions had a statistically significant shorter PFS (HR: 0.38 [95% CI: 0.17–0.88], P = 0.023) and OS (HR: 0.41 [95% CI: 0.16–0.98], P = 0.048).

Conclusions

Time-of-day infusion of durvalumab may impact the survival of patients with locally advanced NSCLC. Although prospective studies of the timing of ICIs are needed, efforts towards scheduling infusions before mid-afternoon might be beneficial.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.