Cancer Immunotherapy May Work Better Before 3PM

Mounting evidence suggests that the time of day at which cancer patients receive treatment could impact their outcomes. This effect is likely due to the circadian rhythm-dependent fluctuations in the function of immune cells as well as proteins that regulate their function, also called checkpoints.

In line with this, in a recent meta-analysis, researchers found that patients with various types of advanced cancer who underwent immune checkpoint inhibitor (ICI) infusions earlier in the day survived longer than their counterparts treated in the late afternoons or evenings.¹ Yongchang Zhang, an oncologist at Central South University, sought to determine a specific time window that could help patients achieve the best therapeutic outcome.

In a new study, Zhang and his colleagues discovered that patients with a highly aggressive lung cancer who received treatment before 3PM survived significantly longer than their counterparts who were treated later in the day.² Their findings, published in Cancer, offer an approach to improve immunotherapy outcomes.

“This study has immediate clinical applicability and the potential to transform current treatment protocols for small cell lung cancer,” said Zhang in a statement.

Zhang’s team retrospectively analyzed data from the electronic medical records of approximately 400 patients with extensive-stage small cell lung cancer who underwent both chemotherapy and immunotherapy using an ICI.

To determine the cutoff time for maximum therapeutic benefit, the researchers grouped the time at which patients received treatment in 30-minute increments between 11AM to 4:30PM. For each time window, they used the patients’ survival data to estimate how likely patients were to benefit from treatment before the specific time window. From this analysis, the team discovered that the treatment administration time made the most difference around 3PM, so they established this as the cutoff time.

Conversely, the team tested how the 3PM cutoff impacted patients’ survival. The researchers split patients into “early” and “late” cohorts based on whether their immunotherapy was administered before or after 3PM, respectively. The team found that indeed, patients who received treatment before 3PM survived roughly seven months longer than their counterparts who got their infusions later in the day.

Zhang believes that “adjusting infusion timing is a straightforward and easily implementable intervention that can be adopted across diverse healthcare settings without additional cost.”

Despite the promising results, the pronounced effects the researchers observed did not extend to patient populations which were minorities in the study, such as female patients (10.6 percent), non-smokers (14.9 percent), as well as those whose disease had metastasized to the liver (24.7 percent). The researchers acknowledged that the underrepresentation of female patients in this work “may limit the generalizability of [their] findings” and must be addressed in future, larger studies.