Research has suggested that cancer treatments administered early in the day are more effective than those administered later in the day. However, most of this work consists of pre-clinical studies, retrospective trials, or meta-analyses.
To validate the implication that cancer treatment works better when given early in the day, a team of researchers conducted a randomized phase 3 trial. The results of the study, recently published in Nature Medicine, demonstrate a marked improvement in outcomes in lung cancer patients who receive treatment early in the day.
The study (NCT05549037) enrolled 210 patients with advanced (stage IIIIC or IV) non-small cell lung cancer (NSCLC). The patients all received the same treatment regimen: four cycles of a PD-1-blocking immunotherapy. The researchers randomized the participants evenly into two treatment cohorts. Half of the patients received treatment before 3:00 PM local time, and the other half received treatment after 3:00 PM.
The researchers published their data when patients had an average follow-up time of just under 2.5 years. At the time of analysis, participants had notably longer progression-free survival time if they received treatment early in the day (average of 11.3 months versus 5.7 months). Similarly, patients receiving treatment early in the day had, on average, 11.2 months longer overall survival than those receiving treatment later in the day. At the end of the study, 45% of the patients in the early treatment group remained alive, compared to around 15% in the late treatment group.
The study reported no significant differences in either treatment-related adverse events or immune-related adverse events between the two treatment groups.
To better understand the mechanism of action, the researchers evaluated the number of circulating CD8+ T cells. The analysis revealed increased numbers of these immune cells in patients treated early in the day. Further, patients treated early in the day exhibited higher proportions of activated CD8+ T cells, while those treated later in the day had higher proportions of exhausted CD8+ T cells. As CD8+ T cells identify and kill cancer cells, their presence generally correlates with a stronger anti-tumor immune response and better efficacy of immune-based therapeutics.
The study provides strong evidence that the time of day affects the efficacy of cancer treatment. Future studies may investigate how the time of day impacts other treatments or other disease sites.