Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Evaluation of efficacy and safety of targeted therapy and immune checkpoint inhibitors in metastatic colorectal cancer
Peng-Jian Wang, Jing Wang, Xue-Min Yao, Wei-Li Cheng, Lu Sun, Jie Yan, Yong-Ling Yu, Su-Yao Li, Da-Peng Li, Jing-Hao Jia
Peng-Jian Wang, Jie Yan, Clinical Medical School, North China University of Science and Technology, Tangshan 063000, Hebei Province, China
Jing Wang, Xue-Min Yao, Yong-Ling Yu, Su-Yao Li, Jing-Hao Jia, Department of Radiochemotherapy, North China University of Science and Technology Affiliated Hospital, Tangshan 063000, Hebei Province, China
Wei-Li Cheng, Da-Peng Li, Department of Digestive Oncology, Tianjin Tumor Hospital Qinhuangdao Hospital, Qinhuangdao 066000, Hebei Province, China
Lu Sun, Department of Radiochemotherapy, Tangshan People’s Hospital, Tangshan 063000, Hebei Province, China
Co-corresponding authors: Da-Peng Li and Jing-Hao Jia.
Author contributions: Li DP and Jia JH contribute equally to this study as co-corresponding authors; Wang PJ and Yan J contributed to patient screening, data collection, and statistical analysis; Wang J, Yao XM, Yu YL, and Li SY conceptualized and designed the study; Jia JH provided important inputs for statistical modeling and manuscript revision; Li DP directed the whole project and ensured funding; Cheng WL and Sun L ensured clinical coordination and compliance with ethical standards; the first draft was written by Wang PJ; Wang PJ, Wang J, Yao XM, Cheng WL, Sun L, Yan J, Yu YL, Li SY, Li DP, Jia JH participated in the review and editing of the manuscript.
Supported by Hebei Provincial Medical Science Research Project Program, No. 20240164.
Institutional review board statement: This investigation was approved by the Ethics Committee of the North China University of Science and Technology Affiliated Hospital (Approval No.202409300002).
Informed consent statement: The need for patient consent was waived due to the retrospective nature of the study.
Conflict-of-interest statement: The authors declare no conflicts of interest related to this manuscript.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Da-Peng Li, Chief Physician, Department of Digestive Oncology, Tianjin Tumor Hospital Qinhuangdao Hospital, No. 64 Guangming Road, Haigang District, Qinhuangdao 066000, Hebei Province, China.
15232330077@163.com
Received: January 9, 2025
Revised: March 7, 2025
Accepted: March 25, 2025
Published online: May 15, 2025
Processing time: 126 Days and 9.6 Hours
BACKGROUND
Colorectal cancer (CRC) is among the most prevalent and deadly cancers globally, particularly in China. Treatment challenges remain in advanced and metastatic cases, especially in third- and fourth-line settings. The combination of targeted therapies with immune checkpoint inhibitors (ICIs) has shown potential in addressing the limitations of single-agent treatments.
AIM
To evaluate the efficacy and safety of targeted therapy (TT) alone and in combination with ICIs for metastatic CRC (mCRC).
METHODS
A multicenter retrospective observational study was conducted to evaluate the efficacy and safety of TT alone and in combination with ICIs for mCRC. A total of 99 patients treated with regorafenib or fruquintinib, with or without ICIs, were enrolled. Propensity score matching (PSM) and inverse probability weighting (IPW) were employed to balance baseline characteristics. The primary endpoint was progression-free survival (PFS), while overall survival (OS) and safety were secondary.
RESULTS
Patients who received combined therapy showed significantly longer median PFS rates compared to those who underwent TT in all analyses (original: 6.0 vs 3.4 months, P < 0.01; PSM: 6.15 vs 4.25 months, P < 0.05; IPW: 5.6 vs 3.3 months, P < 0.01). Although the median OS showed a trend toward improvement in the combination group, the difference was insignificant. Cox regression analysis revealed that combining TT with ICIs significantly reduced the risk of disease progression (hazard ratio = 0.38, P < 0.001). Adverse events (AEs) were generally manageable with both regimens, while serious AEs (grade 3-4) were primarily hypertension, fatigue, and reduced platelet counts. All AEs were controlled effectively by symptomatic treatment or discontinuation of the drug, and no treatment-related deaths were observed.
CONCLUSION
The combination of TT with ICIs offers a significant advantage in terms of PFS for patients with advanced mCRC, accompanied by a favorable safety profile. These findings underscore the benefits of combination therapy in this setting, warranting further investigation in larger prospective clinical trials.
Core Tip: This study demonstrates that combining targeted therapy with immune checkpoint inhibitors significantly improves progression-free survival in patients with metastatic colorectal cancer (mCRC). The study also highlights the manageable safety profile of the combination therapy, offering a potential new approach for advanced mCRC treatment. Further research is needed to confirm these findings in larger trials.
