Treatment Efficacy of Immune Checkpoint Inhibitors for Patients with Advanced or Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

The treatment efficacy of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) has been reported heterogeneously across clinical trials. We conducted a systematic review and meta-analysis to evaluate the efficacy of ICIs in patients with advanced/metastatic CRC. Ovid-Medline was searched to identify clinical trials providing the efficacy outcomes of overall response rate (ORR) or disease control rate (DCR). The pooled ORR and DCR were estimated across all studies and subgroups. Meta-regression was performed to find the influencing factors for treatment efficacy. A total of thirty studies (1870 patients) were eligible. The overall ORR and DCR were 20.1% and 58.5%, respectively, but these results were heterogeneous across studies. Multivariate meta-regression revealed that microsatellite phenotype (odds ratio of MSI-H/dMMR versus MSS/pMMR: 1.67, p < 0.001) and drug regimen (odds ratio of monotherapy versus combination therapy: 1.07, p = 0.019) were the source of heterogeneity and also significantly influenced factors for the efficacy of the treatment. Although the efficacy of ICIs as a first-line therapy was higher than that of ICIs as the second- or more-line therapy (ORR: 51.5% vs. 13.4%, DCR: 85% vs. 49.5%), multivariate regression showed that the line of therapy was not a significant factor for the treatment efficacy. Our study suggests that the microsatellite phenotype and drug regimen, rather than the line of treatment, are the primary factors influencing the treatment response among advanced/metastatic CRC patients treated with an ICI-based regimen.