Key Clinical Summary:

• Design/Population: A pooled analysis of 8 international phase 2/3 trials included 3060 patients with advanced or metastatic lung cancer receiving immune checkpoint inhibitors, comparing early (before 12:00 pm) versus late (after 12:00 pm) administration, with propensity score matching to balance baseline characteristics.
• Key Outcomes: In the primary cohort, median overall survival was 18.5 months and 15.7 months, respectively. In the matched analysis, median OS was 17.3 and 16 months, respectively, meeting non-inferiority criteria. There were similar mortality rates between groups.
• Clinical Relevance: Timing of immune checkpoint inhibitor administration within the day does not meaningfully impact survival, supporting flexibility in treatment scheduling and suggesting that chronotherapy is unlikely to influence outcomes in advanced lung cancer.

Results from the i-TIMES study suggest that the timing of immune checkpoint inhibitor administration does not significantly impact overall survival (OS) results among patients with advanced or metastatic lung cancer.

These results were presented at the European Lung Cancer Congress in Copenhagen, Denmark, by Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

In this large, propensity-score matched analysis, researchers collected data from 3060 patients enrolled across 8 international phase 2/3 randomized trials who received ≥2 cycles of immune checkpoint inhibitor therapy with documented administration timing. Based on the start times from the first 2 treatment cycles, patients were classified as either early (before 12:00 pm; n = 1244), late (after 12:00 pm; n = 964), or mixed (n = 852). When balanced for gender, PD-L1 status, and presence of baseline liver and brain metastases the matched cohort included 1550 patients classified as either early (n = 775) or late (n = 775). 

At a median follow-up of 42.6 months, median OS was 18.5 months in the early arm and 15.7 months in the late arm. There were 567 reported deaths in the early arm and 573 in the late arm. In the matched cohort, median OS was 17.3 months and 16 months, respectively.  The hazard ratio for OS in the matched analysis was 1.039, meeting the predefined criterion for non-inferiority. 

As Dr Peters concluded, “these findings demonstrate that [immune checkpoint inhibitor] treatment timing within the day is unlikely to be a critical determinant of outcomes in [lung cancer] pts, helping to address ongoing uncertainties regarding chronotherapy in this setting while supporting flexibility in clinical practice.” 

Source:

Peters S.  ETOP-Roche i-TIMES: Immunotherapy timing investigation on lung cancer survival. Presented at European Lung Cancer Congress. March 28 - 28, 2026. Copenhagen, Denmark. LBA2.