Clinical benefits of PD-1/PD-L1 inhibitors in patients with metastatic colorectal cancer: a systematic review and meta-analysis

• Published in: World journal of surgical oncology Vol. 20; no. 1; pp. 93 - 13
• Main Authors: Zhang, Xiao, Yang, Zhengyang, An, Yongbo, Liu, Yishan, Wei, Qi, Xu, Fengming, Yao, Hongwei, Zhang, Zhongtao
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24.03.2022; BioMed Central; BMC
• Subjects: Apoptosis; B7-H1 Antigen; Cancer; Cancer therapies; Care and treatment; Clinical efficacy; Clinical trials; Colonic Neoplasms - drug therapy; Colorectal cancer; Colorectal carcinoma; Colorectal neoplasms; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Development and progression; Diagnosis; Disease control; FDA approval; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Inhibitors; Lymphocytes; Medical prognosis; Meta-analysis; Metastases; Metastasis; Microsatellite instability; Mismatch repair; Monoclonal antibodies; Patients; PD-1 protein; PD-L1 protein; Pembrolizumab; Programmed Cell Death 1 Receptor; Prospective Studies; Safety; Statistical analysis; Subgroups; Systematic review; Testing; Tumors; China; Immune checkpoint inhibitors; Colorectal neoplasms; Clinical efficacy; Meta-analysis
• ISSN: 1477-7819; 1477-7819
• DOI: 10.1186/s12957-022-02549-7

Immunotherapy for colorectal cancer has developed rapidly in the past decade. Many high-quality clinical trials examining the application of PD-1/PD-L1 inhibitors in patients with metastatic colorectal cancer (mCRC) have been conducted in recent years. However, the clinical benefits, including the efficacy and safety of these treatments against mCRC, remain controversial. Hence, we conducted this meta-analysis on the clinical benefits of PD-1/PD-L1 inhibitors in patients with mCRC. We searched online databases including MEDLINE, Embase, Cochrane Library, and Web of Science, from inception to January 4, 2021. The outcomes related to efficacy and safety were extracted and analyzed. Subgroup analyses were conducted according to the categories of dMMR-MSI-H (tumors with mismatch repair deficiency and high levels of microsatellite instability) ≥ 5% vs. dMMR-MSI-H < 5%, monotherapy vs. combination therapy, PD-1 inhibitors vs. PD-L1 inhibitors, and nivolumab vs. pembrolizumab. Fourteen studies including 1129 subjects were included in our systematic review. The overall complete response (CR), partial response (PR), stable disease (SD), and progression of disease (PD) rates were 0.01 (95% CI 0.00-0.04), 0.04 (95% CI 0.05-0.26), 0.27 (95% CI 0.22-0.32), and 0.44 (95% CI 0.30-0.58), respectively. The overall objective response rate (ORR) and disease control rate (DCR) were 0.16 (95%CI 0.06-0.31) and 0.50 (95%CI 0.35-0.65), respectively. The overall rate of adverse events (AEs) and severe adverse responses (SAEs) were 0.84 (95% CI 0.72-0.92) and 0.30 (95% CI 0.20-0.41), respectively. The ORRs of the dMMR-MSI-H ≥ 5% and dMMR-MSI-H < 5% subgroups were 0.40 (95% CI 0.30-0.51) and 0.04 (95% CI 0.00-0.09), respectively. PD-1/PD-L1 inhibitors produced encouraging clinical benefits including the response rate in the treatment of dMMR-MSI-H mCRC. They actually have been influenced by the present state of mCRC therapy including pMMR-MSI-L mCRC. Nevertheless, additional multi-center prospective studies are still expected. We have registered this study in the International Prospective Register of Systematic Reviews (PROSPERO), and the registration number is CRD42021249601 .