News release

From: Springer Nature

Medicine: Morning immunochemotherapy may improve lung cancer outcomes

Patients with advanced lung cancer who received immunochemotherapy before 15:00 (3 p.m.) had a more delayed disease progression than patients receiving treatment later in the day. The findings, published as part of a randomised phase 3 trial of 210 participants in Nature Medicine, suggest that scheduling therapy early in the day may offer a simple, cost-neutral way to enhance standard care.

Circadian rhythms, the internal 24-hour clock, are known to affect immune cell behaviour and responses to treatment. Previous retrospective studies across cancers, such as kidney cancer and malignant melanoma, have hinted that administering immune checkpoint inhibitors earlier in the day might be more effective. However, prospective randomised controlled trials to validate these preliminary findings have been lacking.

Yongchang Zhang and colleagues conducted a randomised phase 3 study involving 210 patients with advanced non–small-cell lung cancer who have not received any treatment (treatment-naïve). Patients were assigned to receive immunochemotherapy either before 15:00 (early group) or at or after 15:00 (late group) for the first four treatment cycles. After a median follow-up of approximately 28.7 months, the early group did not experience their cancer worsen (progression-free survival) for an average of 11.3 months, versus 5.7 months for the late group. Median overall survival was 28.0 months in the early group and 16.8 months in the late group. Treatment response rates were 69.5% in the early group and 56.2% in the late group, and there were no significant differences in immune-related adverse events. Through further analysis, the authors also observed more CD8⁺ T cells circulating in the blood (a type of immune cell) and a higher ratio of activated to exhausted CD8⁺ T cells in the early group than in the late group, which could explain higher therapy efficacy in this group.

The authors note that further research is needed to determine long-term survival outcomes. A key limitation of the study is that the patient population was exclusive to China. The mechanistic pathways linking circadian timing to efficacy in patients also require further investigation.