The effect of dosing sequence of programmed death receptor-1 inhibitors combined with chemotherapy on adverse effects in the real world

Haochun TANG^1*Jun Meng^1*Ziyuan Zhou¹Yuelin Zhang²Jun Pan³

• ¹National Cancer Center, Cancer Hospital Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
• ²Guangdong Medical University School of Pharmacy, Dongguan, China
• ³Peking University Shenzhen Hospital, Shenzhen, China

Objective: This study aims to explore the impact of different dosing sequences on the occurrence of adverse events (AEs) when PD-1 inhibitors are combined with chemotherapy, so as to provide a basis for optimizing clinical medication regimens. Methods: Retrospective cohort study and retrospective analysis were conducted on 400 cases of tumor patients who received PD-1 inhibitors combined with chemotherapy in a specialized oncology hospital from January to December 2024. They were divided into two groups according to the dosing sequence: 200 cases in the post-chemotherapy group (PD-1 inhibitors administered first followed by chemotherapy) and 200 cases in the pre-chemotherapy group (chemotherapy administered first followed by PD-1 inhibitors). The baseline characteristics, incidence, types and grades of adverse events in the two groups were counted, and the differences between the groups were compared. Results: Among the 400 patients, males accounted for 63.5%, people aged 40-69 accounted for 72.5%, and the main diseases were lung cancer (28.5%), hepatocellular carcinoma (15.0%) and gastric cancer (10.5%). The total incidence of adverse events was 65.0%, among which the incidence of adverse events in the pre-chemotherapy group (75.0%) was significantly higher than that in the post-chemotherapy group, and the difference was statistically significant (P<0.05). The main types of adverse events were hematological toxicity (22.25%), hepatotoxicity (21.25%) and dermatotoxicity (13.5%). There was no statistically significant difference in the incidence of the same type of adverse events between the two groups (P>0.05). The toxicity grading was mainly G1-G2 (316 cases, 79.0%), and G3 and above accounted for 11.5%. There was no significant difference in the grading distribution between the two groups (P>0.05). Conclusion: The dosing sequence of PD-1 inhibitors combined with chemotherapy is closely related to the occurrence of adverse events. Administering PD-1 inhibitors first can reduce the risk of adverse events, and the choice of dosing sequence should be paid attention to in clinical practice.