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A multi-center research team led by Professor Zhang Yongchang from Hunan Cancer Hospital and supported by The Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine) has discovered that immunochemotherapy administered before 3 p.m. significantly enhances efficacy in advanced lung cancer patients, nearly doubling the progression-free survival (PFS) and increasing the median overall survival (OS) by almost 70%. The study demonstrates that the timing of treatment has a profound impact on treatment outcomes. The findings have been published in the internationally renowned medical journal Nature Medicine.

Lung cancer is the deadliest cancer worldwide and remains the most common and deadliest cancer in Hong Kong, with over 6,000 new cases each year. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers.

Immunotherapy, alternatively called immune checkpoint inhibitor, helps the immune T-cell to recognise the presence of cancer and eliminate it. Multiple randomised studies have confirmed the use of combination of chemotherapy and immunotherapy as standard first-line therapy for patients with advanced stage NSCLC. The human circadian clock is closely associated with immune function and prior retrospective studies suggested that application of immunotherapy according to circadian cycle may optimise treatment efficacy.

Professor Tony Mok Shu-kam, Li Shu Fan Professor of Clinical Oncology, Associate Dean (Translation and Entrepreneurship) and Chairman of the Department of Clinical Oncology at CU Medicine, worked with Professor Zhang Yongchang from Hunan Cancer Hospital leading a multi-center study that enrolled 210 patients with advanced NSCLC from China between 2022 to 2024. The patients were randomly assigned to receive treatment before and after 3 p.m., respectively. The findings after nearly 29 months of treatment are summarised as below:

No significant difference in adverse events was observed between the two cohorts during the research period. Comparing with those treated in the afternoon, the risk of disease progression and risk of death in those treated in the morning decreased by 60%, respectively.

Researchers also observed that the number of anti-tumour CD8⁺ T cells increased in patients treated in the morning but the number of these cells declined in those treated in the afternoon. This suggests that administering treatment in the morning may be more conducive to activating and enhancing the immune response, thereby improving therapeutic efficacy.

As co-corresponding author of the study, Professor Mok said: “The study represents the first large-scale prospective randomised study to establish a direct association between the human biological clock and the effectiveness of cancer immunotherapy. 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 patient or healthcare system.”

Professor Mok also highlighted that as all participants in this study were Chinese patients, further international research is needed to verify the impact of circadian administration of immunotherapy across multiple populations. Furthermore, future clinical studies involving immunotherapy should document treatment timing and consider incorporating infusion time as a stratification factor in their analyses.