Despite research suggesting that giving immunotherapy in the morning is more effective than later in the day, a new analysis of patients with lung cancer finds no such benefit.

The findings, presented at the European Lung Cancer Congress (ELCC) 2026, are based on over 3000 patients who received immune checkpoint inhibitor therapy in a clinical trial setting. It found that infusion time of day made no difference in patients’ overall survival.

“In this context, any potential chronotherapy effect appears limited in magnitude and of uncertain clinical relevance,” said presenter Solange Peters, MD, PhD, chair in the medical oncology and the thoracic malignancies program at University Hospital of Lausanne in Lausanne, Switzerland.

“Altogether,” she said, “these findings support a flexible and pragmatic approach to treatment scheduling, without compromising clinical outcomes.”

Peters opened her presentation by noting that the timing of immunotherapy administration is primarily determined by organizational and planning constraints that are particular to each outpatient infusion center.

However, Peters said, there has been growing interest in chronotherapy — a strategy that aims to leverage the “principle of circadian biology” to optimize the timing of medical treatments.

She pointed out that immune checkpoint inhibitors rely on adaptive immune activation, which is driven by cell-intrinsic circadian oscillators that regulate dendritic cells and leukocyte trafficking, as well as CD8+ T-cell activation through the rhythmic control of chemokine signaling and immune gene expression.

Preclinical and translational data indicate there is greater immune activation in the morning, leading to the hypothesis that the morning administration of immunotherapy could improve clinical outcomes.

And retrospective research has appeared to back that up. Peters noted that more than 30 such studies have linked earlier-in-the-day immunotherapy to improved progression-free and overall survival among patients with a range of cancer types — with meta-analyses finding a reduction in the risk for mortality of approximately 50%.

To investigate further, Peters and her colleagues examined individual patient-level data from Roche-sponsored phase 2 and 3 randomized trials of patients with lung cancer treated with an immune checkpoint-based strategy with atezolizumab vs chemotherapy.

The patients were classified as receiving their first two immunotherapy doses either early (defined as before 12 PM) or late (after 12 PM). They were then matched by their study propensity score based on gender, the presence of liver or brain metastases, or PD-L1 status.

Eight trials were included in the primary analysis, in which 3060 patients received at least two validated immunotherapy infusions, including 1244 (41%) patients treated early, 964 (32%) late, and 852 (28%) who were on a mixed schedule of morning and afternoon administration.

After propensity score matching, the researchers were left with 775 patients treated early and the same number in the late group. Patients in the early group were older, at a median age of 65 years vs 62 years, but there were no differences between the groups in terms of performance status, tumor histology, PD-L1 status, or the presence of liver or brain metastases.

There were a total of 1140 deaths across the studies, and the primary analysis showed that the hazard ratio for overall survival between early and late immunotherapy was a nonsignificant at 1.039 (95% CI, 0.925-1.168).

At a median follow-up of roughly 41 months, the median overall survival was 17.3 months with early administration vs 16 months with late treatment, at a total number of deaths of 567 (73%) vs 573 (74%).

Similar results were seen in the overall unmatched cohort, where the median overall survival was 18.5 months with early administration, 15.7 months with late, and 18.2 months with a mixed approach. Again, the hazard ratio for early vs late administration was nonsignificant at 1.088 (95% CI, 0.982-1.207).

When the researchers conducted sensitivity analyses based on gender, performance status, and the presence of metastases, timing of immunotherapy made no difference in overall survival in the matched cohort.

However, Peters reported that was not the case in the unmatched cohort — which, she added, underscores the importance of matching in this type of analysis.

Commenting on the results, Jhanelle E. Gray, MD, of Moffitt Cancer Center in Tampa, Florida, said there may be some fundamental differences between patients who receive treatment in the morning vs later in the day. Patients who are generally healthier and have more resources may, for example, have flexible job schedules or better access to transportation or childcare that allow them to receive treatment early in the day.

Gray also pointed out that the half-life of immune checkpoint inhibitors is approximately 3-4 weeks, which means their concentrations remain high for days to weeks, not just for hours.

“Therefore, the time of day of the administration should have minimal influence on circulating drug levels at the time of immune engagement,” she said. “If we give a drug in the PM, should the drug not be around in the morning, when the immune system becomes more active?”

While most evidence supporting a benefit from early immunotherapy comes from retrospective research, one randomized trial garnered headlines earlier this year when it showed that giving anti-PD-1 therapy before 3 PM rather than after greatly improved survival outcomes among patients with lung cancer.

However, that study, published in Nature Medicine, quickly came under fire for issues with the data. It now contains an Editor’s Note saying that those concerns are under investigation, Gray pointed out.

As it stands, she said, evidence remains “insufficient to support adopting early time-of-day immune checkpoint inhibitor dosing in routine practice.”

The researchers disclosed no funding for the study. Peters reported having financial relationships with numerous companies, including AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, and Roche/Genentech. Gray had no disclosures.