Clinical evaluation of sintilimab in conjunction with bevacizumab for advanced colorectal cancer with microsatellite stable-type after failure of first-line therapy

Liang Wang; Yong-Zhi Diao; Xin-Fu Ma; Yu-Shuang Luo; Qi-Jing Guo; Xiao-Qian Chen

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

World J Gastrointest Surg. 2024 Oct 27;16(10):3277-3287. doi: 10.4240/wjgs.v16.i10.3277.

Authors

Liang Wang¹, Yong-Zhi Diao², Xin-Fu Ma¹, Yu-Shuang Luo³, Qi-Jing Guo³, Xiao-Qian Chen⁴

Affiliations

¹ Department of Gastrointestinal Oncology Surgery, Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China.
² Department of Gastroenterology, The First People's Hospital of Xining, Xining 810000, Qinghai Province, China.
³ Department of Medical Oncology, Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China.
⁴ Department of Gastrointestinal Oncology Surgery, Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China. cxq925@163.com.

Abstract

Background: At present, immune checkpoint inhibitors (ICIs) remain the 1^st-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 1^st-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 1^st-line therapy.

Keywords: Bevacizumab; Cancer-associated fibroblasts; Colorectal cancer; Cytotoxic T lymphocytes; Immune checkpoint inhibitors; Tumor-associated macrophages.