Impact of time-of-day infusion of camrelizumab combined with chemotherapy on efficacy in advanced malignant tumors.

person Li-Yue Sun Department of General Practice, Zhongshan Hospital, Fudan University, Shanghai, Shanghai, China info_outline Li-Yue Sun, Xian Xu, Quan-An Xu, Ke-Xin Xian, Xin-Xin Zeng, Hua-Gen Li, Xu-Hui Zhang

Authors person Li-Yue Sun Department of General Practice, Zhongshan Hospital, Fudan University, Shanghai, Shanghai, China info_outline Li-Yue Sun, Xian Xu, Quan-An Xu, Ke-Xin Xian, Xin-Xin Zeng, Hua-Gen Li, Xu-Hui Zhang Organizations Department of General Practice, Zhongshan Hospital, Fudan University, Shanghai, Shanghai, China, Guangdong Second Provincial General Hospital, Guangzhou, China, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China, Beijing Friendship Hospital, Beijing, China Abstract Disclosures Research Funding the Guangzhou Science and Technology Plan Project the Basic Research Project of Guangzhou Municipal School (Hospital), the Guangdong Second Provincial General Hospital, Doctoral workstation foundation of Guangdong Second Provincial General Hospital, Guangdong Medical Scientific Research, National Natural Science Foundation of China Background: The combination of immune checkpoint inhibitors (ICIs) with chemotherapy has emerged as a standard first-line treatment strategy for advanced cancers. Camrelizumab and Tislelizumab, representative ICIs, have approval by the Chinese NMPA for first-line treatment of advanced cancers such as lung cancer and esophageal cancer. Previous studies have indicated that the timing of drug administration can influence the efficacy of ICIs. However, studies on the ICIs plus chemotherapy are lacking. Therefore, we conducted a retrospective study to explore the effect of the timing of infusion on patients with advanced cancer undergoing treatment with ICIs combined chemotherapy. Methods: We retrospectively enrolled a total of 253 patients diagnosed with advanced cancers between 2017 and 2023 in Guangdong Second Provincial General Hospital. Among these patients, 109 received camrelizumab (Cam cohort) plus chemotherapy and 65 received tislelizumab (Tis cohort) plus chemotherapy. Patients were grouped into morning (AM) and afternoon (PM) categories based on the timing of their ICIs administration (< 1 times versus ≥ 1 times after 16:00). The Response Evaluation Criteria in Solid Tumors Criteria V.1.1 was used to evaluate the response to treatment. The primary endpoint was progression-free survival (PFS). Results: The results consistently showed that the PM group had a longer PFS than the AM group in the overall patients (p < 0.01). In the Cam cohort, the PM group (n = 48) exhibited a longer PFS compared to the AM group (n = 61) (16.8 months vs. -, p = 0.02). However, no significant difference in PFS was observed among patients in the Tis cohort (AM vs. PM, n = 34 vs. n = 31, 16.1 months vs. -, p = 0.51). Subgroup analyses indicated that the PM group had a more favorable PFS treatment effect in most subgroups. The incidence of any Treatment Emerged Adverse Event (TEAE) (Cam cohort, AM vs. PM, 98.52% vs. 92.68%; Tis cohort, AM vs. PM, 97.05% vs. 100.00%) and grade 3 TEAEs (Cam cohort, AM vs. PM, 5.80% vs.7.30%; Tis cohort, AM vs.PM - vs. 12.90%) was similar in the Cam cohort and Tis cohort. The most common adverse events are anemia (Cam cohort vs. Tis cohort, 70.58% vs. 79.41%), thrombocytopenia (Cam cohort vs. Tis cohort, 54.41% vs. 58.82%) and lymphopenia (Cam cohort vs. Tis cohort, 44.11% vs. 44.11%). Conclusions: The findings of this study highlight a significant variation in daily rhythms among advanced cancer patients undergoing treatment with ICIs plus chemotherapy. Interestingly, a trend was observed in patients treated with camrelizumab, where those receiving treatment in the afternoon demonstrated a longer PFS. However, this trend was not observed in patients treated with tislelizumab. These results suggest that time-of-day infusion could potentially serve as a personalized strategy for patients treated with combination ICIs therapy.