Optimizing Nivolumab Efficacy: The Role of Dosing Time in Advanced Non-Small Cell Lung Cancer

BACKGROUND Although immunotherapy has revolutionized lung cancer treatment, its effectiveness as a single agent in the second-line setting is limited by low response rates and the small number of patients who benefit from it, despite its demonstrating superior overall survival compared to standard chemotherapies. This study aimed to determine whether the timing of nivolumab administration, specifically before or after 1 PM, influences treatment efficacy, thereby exploring its potential role in overcoming drug resistance. MATERIAL AND METHODS This single-center retrospective study included 54 patients with stage IV or recurrent non-small cell lung cancer who received nivolumab as second-line therapy between January 2021 and January 2025. Patients were categorized into 2 groups based on whether they received all treatment protocols before or after 1 PM, and treatment outcomes were subsequently compared. RESULTS Patients treated before 1 PM showed statistically significant improvements in treatment response compared to those treated after 1 PM. However, no significant differences were found in progression-free survival or immune-related adverse effects. CONCLUSIONS Our study indicates that the timing of nivolumab administration can affect treatment outcomes, with earlier administration potentially leading to better responses. This observation aligns with the growing body of evidence suggesting that circadian rhythms play a significant role in cancer biology and treatment efficacy. Understanding the mechanisms behind these effects could lead to more effective treatment strategies and improved patient outcomes. Further research is needed to elucidate the underlying mechanisms and validate these findings in larger, prospective studies. Despite the lack of clear guidelines, our findings, along with other studies, suggest earlier immunotherapy administration may be beneficial.