Reacción a "Administering immunotherapy and chemotherapy in the morning could improve their effectiveness against lung cancer"

It is a good article published in one of the best journals in the field. The article presents part of a phase 3 randomised trial with 210 participants and suggests that scheduling therapy early in the day may offer a simple and inexpensive way to improve standard care.

Circadian rhythms, the internal 24-hour clock, are known to affect immune cell behaviour and response to treatment, especially with therapies that require the immune system to act, such as immunotherapy. Previous retrospective studies on cancers suggest that administering immunotherapy (checkpoint inhibitors) early in the day may be more effective. However, no prospective randomised controlled trials have been conducted to validate these preliminary findings.

The authors conducted a prospective, randomised phase 3 study involving 210 patients with advanced non-small cell lung cancer who had not previously been treated. Patients were assigned to receive immunochemotherapy before 15:00 (early group) or at 15:00 or later (late group) during the first four cycles of treatment. After a follow-up of approximately 28.7 months, the late group showed no worsening of cancer (progression-free survival, PFS) for an average of 5.7 months, while the early group remained without worsening cancer (PFS) for almost twice as long, an average of 11.3 months. The median overall survival was 28 months in the early group and 16.8 months in the late group. Treatment response rates were also higher in the early group than in the late group, and no significant differences in immune-related adverse events were observed. In other words, treatment in the morning appears to be more effective (almost twice as effective) than treatment in the afternoon.

In principle, this is a well-controlled study with clear results based on the data provided.

It was known that circadian rhythms affect immune cell behaviour and response to treatment. Previous retrospective studies on cancers such as kidney cancer and malignant melanoma have suggested that administering immunotherapy (checkpoint inhibitors) early in the day may be more effective. However, no prospective randomised controlled trials have been conducted to validate these preliminary findings. The result of this trial, as the authors say, opens the door (if these results are validated elsewhere/in other hospitals) to increasing the efficacy of immunotherapy in a simple way, simply by changing the time of administration of the therapy.

The authors observed more CD8⁺ T cells circulating in the blood (a type of immune cell) and a higher proportion of activated versus exhausted CD8⁺ T cells in the early treatment group than in the late treatment group, which could explain the greater efficacy of the therapy in this group. Although these are preliminary results and need to be confirmed and supplemented with the correct mechanism of action, it could explain the results, since, for example, rest or the body's metabolic state due to the circadian clock in the early hours could justify a better immune component that would help in treatment processes with immunotherapies.

The most important limitations are, for example, that the patient population was focused exclusively on China, requiring validation in other countries and contexts to extend the findings to patients in general. In addition, more research is needed to present overall survival data and, above all, the mechanism of how and why this phenomenon occurs, or factors that may interfere with it.