Wang L, Diao YZ, Ma XF, Luo YS, Guo QJ, Chen XQ. Clinical evaluation of sintilimab in conjunction with bevacizumab for advanced colorectal cancer with microsatellite stable-type after failure of first-line therapy. World J Gastrointest Surg 2024; 16(10): 3277-3287 [PMID: 39575283 DOI: 10.4240/wjgs.v16.i10.3277]
Corresponding Author of This Article
Xiao-Qian Chen, Attending Doctor, Department of Gastrointestinal Oncology Surgery, Affiliated Hospital of Qinghai University, No. 29 Tongren Road, West District, Xining 810000, Qinghai Province, China. cxq925@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Randomized Controlled Trial
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Wang L, Diao YZ, Ma XF, Luo YS, Guo QJ, Chen XQ. Clinical evaluation of sintilimab in conjunction with bevacizumab for advanced colorectal cancer with microsatellite stable-type after failure of first-line therapy. World J Gastrointest Surg 2024; 16(10): 3277-3287 [PMID: 39575283 DOI: 10.4240/wjgs.v16.i10.3277]
World J Gastrointest Surg. Oct 27, 2024; 16(10): 3277-3287 Published online Oct 27, 2024. doi: 10.4240/wjgs.v16.i10.3277
Clinical evaluation of sintilimab in conjunction with bevacizumab for advanced colorectal cancer with microsatellite stable-type after failure of first-line therapy
Liang Wang, Xin-Fu Ma, Xiao-Qian Chen, Department of Gastrointestinal Oncology Surgery, Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
Yong-Zhi Diao, Department of Gastroenterology, The First People’s Hospital of Xining, Xining 810000, Qinghai Province, China
Yu-Shuang Luo, Qi-Jing Guo, Department of Medical Oncology, Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
Co-first authors: Liang Wang and Yong-Zhi Diao.
Author contributions: Chen XQ contributed to the study concept and design, revised and reviewed the manuscript; Wang L and Diao YZ co-wrote the manuscript, sharing the first authorship; Ma XF collected the data and reviewed the literature; Wang L was responsible for the data analysis and making figure; Guo QJ was responsible for the experimental operation; Luo YS contributed to the study concept; Chen XQ is the guarantor of this study; All authors contributed to the article and approved the submitted version.
Supported bythe 2021 Key Topic of the Qinghai Provincial Health System-Guiding Plan Topic, No. 2021-WJZDX-43.
Institutional review board statement: The study was reviewed and approved by the Affiliated Hospital of Qinghai University Institutional Review Board, No. SL-2021170.
Clinical trial registration statement: As the author’s organization and ethics committee did not require clinical trial registration prior to the study, this study was not registered.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The raw data supporting the conclusions of this article will be made available by the authors without undue reservation.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Corresponding author: Xiao-Qian Chen, Attending Doctor, Department of Gastrointestinal Oncology Surgery, Affiliated Hospital of Qinghai University, No. 29 Tongren Road, West District, Xining 810000, Qinghai Province, China. cxq925@163.com
Received: April 25, 2024 Revised: August 28, 2024 Accepted: September 14, 2024 Published online: October 27, 2024 Processing time: 155 Days and 15.5 Hours
Abstract
BACKGROUND
At present, immune checkpoint inhibitors (ICIs) remain the 1st-line therapy method for patients suffering from high microsatellite instability /deficient mismatch repair metastatic colorectal cancer (mCRC). However, ICI treatments demonstrate minimal therapeutic efficacy against microsatellite stable (MSS)/proficient mismatch repair (pMMR) CRC. This is mainly because this type of tumor is a “cold tumor” with almost no lymphocyte infiltration. Anti-angiogenic drugs have been found to improve the immune microenvironment by promoting many immune cells to enter the immune microenvironment, thereby exerting anti-tumor effects.
AIM
To investigate the effects of ICIs combined with bevacizumab monoclonal antibody on tumor immune cells in MSS/pMMR advanced CRC patients with first-line treatment failure.
METHODS
A total of 110 MSS/pMMR patients with advanced CRC after first-line treatment failure in the Affiliated Hospital of Qinghai University were enrolled for a randomized controlled trial. In short, patients in the experimental group (n = 60) were given sintilimab plus bevacizumab for 4 cycles, and those in the control group (n = 50) patients were treated with FOLFIRI combined with bevacizumab for 4 cycles. The expression levels of cluster of differentiation (CD) 8 (+) T cells, tumor-associated macrophages (TAMs), and cancer-associated fibroblasts (CAFs) were comprehensively evaluated to assess the effects of sintilimab combined with bevacizumab on MSS/pMMR advanced CRC sufferers following failure of 1st-line therapy.
RESULTS
The positive expression rates of CD8 (+) T lymphocytes (30% vs 50%), TAMs (23.30% vs 60%), and CAFs (23.30% vs 50%) before and after treatment in both groups exhibited statistical significance (P < 0.05). Additionally, the therapeutic effects of both groups (partial remission: 26.67% vs 10%; objective response rate: 26.70% vs 10%) were significantly different (P < 0.05). Although the experimental group showed a higher progression-free survival, median progression-free survival, and disease control rate than the control group, the difference was not statistically significant. Moreover, no significant difference in the occurrence rate of drug-related adverse reactions after treatment between the two groups was found (P > 0.05).
CONCLUSION
ICIs in combination with bevacizumab can not only improve the patient’s prognosis but also yield safe and controllable adverse drug reactions in patients suffering from MSS/pMMR advanced CRC after failure to a 1st-line therapy.
Core Tip: In this study, immune checkpoint inhibitors (ICIs) in combination with bevacizumab were applied to microsatellite stable (MSS)/proficient mismatch repair (pMMR) colorectal cancer (CRC) patients with first-line treatment failure. It was found that ICIs combined with bevacizumab treatment significantly changed the tumor immune cells compared with the pre-treatment period. Additionally, ICIs combined with bevacizumab not only further improved their clinical efficacy compared with ordinary chemotherapy combined with anti-angiogenic drugs, but also yielded safe and controllable adverse drug reactions, which provided a new option for MSS/pMMR CRC patients experiencing 1st-line treatment failure.
