Hong Kong – A new study is suggesting a simple adjustment to cancer treatment schedules could significantly improve outcomes for patients with advanced non-small cell lung cancer. Researchers have found that administering immunochemotherapy earlier in the day – before 3:00 PM – leads to substantially improved progression-free survival and overall survival rates.
The findings, led by academics at Hunan Cancer Hospital in mainland China and supported by the Chinese University of Hong Kong’s faculty of medicine, represent the first randomized study to demonstrate a clear difference in outcomes based on the time of day immunochemotherapy is infused. The research, published in Nature Medicine, indicates that early administration nearly doubled progression-free survival and increased median overall survival by almost 70 percent.
“The findings are highly encouraging as a simple adjustment to the timing of treatment may enhance therapeutic efficacy and improve survival at no additional cost to the patient or healthcare system,” said Professor Tony Mok Shu-kam, chairman of the department of clinical oncology at Chinese University and co-corresponding author of the study, speaking on .
The phase 3 LungTIME-C01 trial involved 210 patients with treatment-naive stage IIIC-IV non-small cell lung cancer (NSCLC) lacking driver mutations. Participants were randomly assigned to receive immunochemotherapy either before or after 3:00 PM over the first four treatment cycles. After a median follow-up of 28.7 months, the results showed a median progression-free survival of 11.3 months in the early time-of-day group, compared to 5.7 months in the late time-of-day group. This corresponded to a hazard ratio for earlier disease progression of 0.40 (95% confidence interval: 0.29–0.55; P < 0.001).
the median overall survival was 28.0 months in the early group, versus 16.8 months in the late group, with a hazard ratio of 0.42 (95% confidence interval: 0.29–0.60; P < 0.001). The objective response rate was also higher in the early treatment group, at 69.5% compared to 56.2% in the late group (P = .046). Researchers found that time of day treatment administration and PD-L1 tumor proportion score were the only factors that significantly predicted progression-free and overall survival outcomes.
The study builds on a growing body of evidence suggesting a link between circadian rhythms and cancer treatment efficacy. Over 20 retrospective studies have indicated that administering single-agent immune checkpoint inhibitors earlier in the day can lead to a near doubling in progression-free and/or overall survival in patients with advanced or metastatic cancer, including NSCLC. The LungTIME-C01 trial is significant because This proves the first prospective, randomized controlled trial to validate these findings.
The mechanism behind this phenomenon appears to be related to the body’s natural circadian rhythms and their impact on the immune system. The research showed that morning circulating CD8+ T cells increased in the early time-of-day group, while they declined in the late group (P < 0.001). The ratio of activated versus exhausted CD8+ T cells was also higher in the early group (P < 0.001). CD8+ T cells are crucial components of the immune system responsible for identifying and destroying cancer cells. The findings suggest that immunochemotherapy is more effective when administered when the immune system is naturally more active.
While the study focused specifically on non-small cell lung cancer, experts believe the findings could have broader implications for the treatment of other cancers. The relatively low cost and ease of implementation – simply adjusting treatment schedules – make this a potentially impactful change for cancer care globally. However, Professor Mok cautioned that further research is needed to determine whether these findings apply to all types of cancer and all immunotherapies.
Treatment-related adverse events were consistent with established safety profiles for immunochemotherapy, and no new safety signals were observed. Importantly, there were no significant differences in immune-related adverse events between the two groups, suggesting that adjusting the time of day does not compromise patient safety.
The study, identified as NCT05549037, was conducted across multiple centers and involved a rigorous methodology. The results are expected to prompt a re-evaluation of treatment protocols for NSCLC and potentially other cancers, with healthcare providers considering the optimal time of day for immunochemotherapy administration to maximize patient benefit. The findings also underscore the growing importance of chronotherapy – the practice of timing treatments to coincide with the body’s natural rhythms – in modern oncology.
