Patient deaths could be halved by simply adjusting the timing of immunotherapy treatment.
Receiving a cancer immunotherapy treatment earlier in the day could have the same benefits as taking an additional drug — without the toxic side effects.
Scientists in China tested how the timing of immunotherapy could influence its efficacy in patients with advanced stages of one of the most aggressive forms of lung cancer, known as small cell lung cancer. They found that patients who were treated before 3pm had a 52% lower risk of cancer progression and a 63% lower risk of death.
“Adjusting infusion timing is a straightforward and easily implementable intervention that can be adopted across diverse healthcare settings without additional cost,” said Yongchang Zhang, researcher at Central South University, who led the study. “This study has the potential to transform current treatment protocols for small cell lung cancer.”
These striking results add to the growing body of evidence that the circadian rhythm—the biological clock that regulates the sleep-wake cycle—can have a significant impact on the strength of certain medications.
Finding the optimal treatment window
Small cell lung cancer is a relatively rare type of lung cancer known for growing and spreading very fast, meaning it is often in advanced stages by the time it is caught. As a result, most patients do not survive for longer than a year after receiving a diagnosis.
While immunotherapy has significantly improved survival and remission rates, not every patient responds fully—or sometimes at all—to these cutting-edge treatments. Researchers across the world are now studying why and looking for ways to boost their efficacy.
Zhang and colleagues looked at past data from 397 lung cancer patients who had been treated with a combination of chemotherapy and immunotherapy at the Affiliated Cancer Hospital of Xiangya School of Medicine at Central South University between May 2019 and October 2023. The researchers calculated the median time at which each patient received their first four immunotherapy infusions, and then determined for how long the treatment was able to stop cancer growth and keep the patient alive.
Statistical analysis revealed that patients treated earlier in the day responded more effectively to treatment, with the optimal cutoff time found to be at 3pm. On average, patients treated before this threshold lived for more than six months longer than those treated later in the day. The positive effects of earlier infusion times were strongest in patients who were male, had a history of smoking, and no liver metastases.
The idea that administering immunotherapy earlier in the day can benefit cancer patients is not entirely new. In recent years, scientists have been documenting this phenomenon across a wide range of cancer types. Although the exact threshold of optimal treatment varies between studies, often ranging from about 12pm to 4pm, the evidence collected so far suggests that earlier treatment times can nearly double the efficacy of immunotherapy.
However, this effect had never been reported before in small cell lung cancer.
“What’s most striking is the extent of the benefit — the highest to date in any cancer,” said Pasquale Innominato, clinical professor at the University of Warwick and medical oncologist at Gwynedd Hospital, who was not involved in the study.
He highlights that the standard chemotherapy treatment for this aggressive cancer has largely remained the same for the past 30 years. Immunotherapies have only been available to these patients for about five years, and they often just extend survival by a couple of months.
In contrast, adjusting the timing of immunotherapy could more than halve the risk of early death, therefore potentially surpassing the benefits of adding that immunotherapy drug to a patient’s treatment plan in the first place. The extent of the benefit is especially remarkable considering that these are very expensive drugs that can have serious side effects.
Attuning to our biological clocks
Research is increasingly uncovering that the genes that make our internal clocks tick control more than just when we are asleep or awake. For instance, immune cells have been reported to change their behavior following 24-hour cycles, often showing stronger anti-cancer activity in the morning. This could be a possible reason why treatments designed to boost the immune response seem to be more effective earlier in the day.
Currently, about half of all immunotherapy infusions are estimated to happen before noon. With growing evidence that treating patients earlier in the day could be an affordable yet very impactful measure, medical institutions around the world are looking into shifting their schedules accordingly.
However, implementing these changes into routine clinical practice can be challenging at a logistical level. Clinics plan treatment schedules around the availability of infusion chairs, which can be limited given that a single immunotherapy session can take up to 90 minutes and potentially extend to several hours when multiple treatments are given at once, for instance when immunotherapies are combined with chemotherapy.
Researchers across Asia, Europe and North America are currently working together to find practical ways of ensuring patients are treated earlier in the day. Some examples include preparing the immunotherapy infusion the evening before and scheduling a phone consultation with the patient the previous day to confirm everything is ready to go as soon as they arrive at their appointment.
Although the first large-scale clinical trials are now starting to confirm these findings, more research will still be needed to properly understand how exactly timing affects the efficacy of immunotherapy. In the future, Innominato sees promise in exploring whether the optimal infusion time changes between patients — think of morning people versus night owls, who have naturally opposed daily rhythms. If differences are found, doctors could one day personalize treatment to each patient based on their unique biological clocks.
Reference: Zhe Huang et al., Overall survival according to time‐of‐day of immunochemotherapy for extensive‐stage small cell lung cancer, Cancer (2025). DOI: 10.1002/cncr.70126
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