Gao Z, Wang XY, Shen ZG, Liu JH, Wang XY, Wu SK, Jin X. Chemotherapy plus bevacizumab with or without anti-programmed death 1 immunotherapy as the second-line therapy in colorectal cancer. World J Gastroenterol 2025; 31(21): 106939 [DOI: 10.3748/wjg.v31.i21.106939]
Corresponding Author of This Article
Shi-Kai Wu, Department of Medical Oncology, Peking University First Hospital, No. 8 Xishiku Street, Beijing 100034, China. skywu4923@sina.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Jun 7, 2025; 31(21): 106939 Published online Jun 7, 2025. doi: 10.3748/wjg.v31.i21.106939
Chemotherapy plus bevacizumab with or without anti-programmed death 1 immunotherapy as the second-line therapy in colorectal cancer
Zhao Gao, Xiao-Yan Wang, Zhi-Gang Shen, Jia-Hua Liu, Xiao-Yun Wang, Shi-Kai Wu, Xuan Jin
Zhao Gao, Xiao-Yun Wang, Shi-Kai Wu, Xuan Jin, Department of Medical Oncology, Peking University First Hospital, Beijing 100034, China
Xiao-Yan Wang, Zhi-Gang Shen, Jia-Hua Liu, Department of Pharmacy, Jilin Cancer Hospital, Changchun 130012, Jilin Province, China
Co-corresponding authors: Shi-Kai Wu and Xuan Jin.
Author contributions: Gao Z collected and analyzed the data; Gao Z and Wang XY wrote the manuscript; Shen ZG, Liu JH, and Jin X analyzed the data; Jin X and Wu SK conceived of the review and edited the manuscript, they contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors read and approved the final manuscript.
Supported by the National High Level Hospital Clinical Research Funding (Multi-center Clinical Research Project of Peking University First Hospital), No. 2022CR65.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Peking University First Hospital (approval No.2023-505-003) and Jilin Cancer Hospital (approval No. 202501-003-01).
Informed consent statement: The informed consent was waived by the Institutional Review Board.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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: Shi-Kai Wu, Department of Medical Oncology, Peking University First Hospital, No. 8 Xishiku Street, Beijing 100034, China. skywu4923@sina.cn
Received: March 11, 2025 Revised: April 23, 2025 Accepted: May 23, 2025 Published online: June 7, 2025 Processing time: 87 Days and 7.3 Hours
Abstract
BACKGROUND
Patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) typically exhibit an immunosuppressive tumor microenvironment and demonstrate a low response rate to immunotherapy. Reports suggest that chemotherapy and anti-angiogenic therapy may have the potential to enhance the response to immunotherapy in these patients. This study aims to evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without anti-programmed death 1 (PD-1) immunotherapy as the second-line regimen for MSS mCRC.
AIM
To evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without anti-PD-1 immunotherapy as the second-line regimen for MSS mCRC.
METHODS
A retrospective analysis was conducted on patients with MSS mCRC diagnosed at Peking University First Hospital and Jilin Cancer Hospital from January 2020 to December 2024. The patients were divided into two groups: The experimental group receiving second-line chemotherapy combined with bevacizumab and anti-PD-1 immunotherapy, and the control group receiving chemotherapy combined with bevacizumab. Propensity score matching was applied to balance potential prognostic factors, including age, gender, Eastern Cooperative Oncology Group score, number of metastases, and primary tumor site. The progression-free survival, overall survival, disease control rate, objective response rate, and treatment-related adverse reactions were compared between the two groups. Kaplan-Meier analysis and log-rank test were used to compare survival outcomes. Inverse probability of treatment weighting was used for sensitivity analysis.
RESULTS
Propensity score matching resulted in 103 matched eligible patients. The median follow-up period was 13.9 months in the matched cohort. The objective response rate was 11.5% and 9% for the experimental and control groups, respectively (P = 0.710), while the disease control rate was 76.9% and 53.2%, respectively (P = 0.058). The median progression-free survival in the experimental group was 8.27 months [95% confidence interval (CI): 6.7-14.7 months], significantly higher than that in the control group, which was 4.63 months (95%CI: 3.9-5.67 months) (hazard ratio = 0.4143, 95%CI: 0.2462-0.6972, P = 0.00066). There was a trend towards the higher median overall survival in the experimental group compared to the control group (hazard ratio = 0.4504, 95%CI: 0.1897-1.07, P = 0.064). The incidences of adverse events were similar between the two groups.
CONCLUSION
Compared with the standard second-line chemotherapy combined with bevacizumab regimen, second-line therapy that combines chemotherapy with bevacizumab and anti-PD-1 immunotherapy has demonstrated promising efficacy in the treatment of MSS mCRC, while exhibiting a similar safety profile.
Core Tip: This manuscript addresses to evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without anti-programmed death 1 immunotherapy as the second-line regimen for microsatellite stable metastatic colorectal cancer. As there is currently no clinical data on the second-line treatment of advanced colorectal cancer with the combination of immunotherapy, anti-angiogenic drugs, and anti-programmed death 1 immunotherapy, we conducted a multicenter retrospective cohort clinical study to explore the safety and efficacy of this triplet therapy in second-line treatment of advanced colorectal cancer patients.
