Evaluation of immune checkpoint inhibitors for colorectal cancer: A network meta‑analysis

Abstract

Colorectal cancer (CRC) is challenging to treat due to its high metastatic rate. Recent strategies have focused on combining immune checkpoint inhibitors (ICIs) with other treatments. The aim of the present study was to conduct a network meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and adverse effects of different ICI treatments for CRC. A literature search for RCTs was conducted using PubMed, the Cochrane Library, Embase, ClinicalTrials.gov and Web of Science databases, covering the period from the inception of each database until April 2024. A total of 12 RCTs involving 2,050 participants were selected for inclusion in the analysis. The network meta-analysis employed the MetaInsight tool to assess multiple endpoints. The criteria for study selection were based on the Population, Intervention, Comparison, Outcome and Studies framework as follows: i) Population, patients with CRC; ii) intervention, studies using ICI to treat CRC; iii) comparison, active comparators, including placebo; iv) outcome, overall survival, progression-free survival, objective response rate and adverse events; and v) study design, RCTs. The results of the analysis revealed that programmed cell death-ligand 1 (PD-L1) inhibitors significantly improved overall survival time [mean difference (MD), 2.28 months; 95% confidence interval (CI), 0.44 to 4.11], while programmed cell death protein 1 (PD-1) inhibitors exhibited a superior progression-free survival time (MD, 4.79 months; 95% CI, 3.18 to 6.40) compared with active comparators. However, none of the ICI treatments had significant differences in odds ratios for the objective response rate and adverse events compared with active comparators. These findings indicate that treatment with PD-L1 and PD-1 inhibitors improved the overall survival time and delayed disease progression in patients with CRC. These findings offer valuable insights for future research aimed at improving CRC patient outcomes.

Keywords: colon; immunotherapy; neoplasm; rectum; survival.

Figure 1.

Network plots illustrating the effects of different pharmacological interventions in patients with colorectal cancer. Network plots for (A) overall survival, (B) progression-free survival, (C) objective response rate and (D) adverse events are shown. The size of the nodes and thickness of edges represent the number of studies that compared two given treatments. Numbers on the lines indicate the number of trials conducted for the comparison. CTLA-4, cytotoxic T-lymphocyte associated protein 4; PD-1, programmed cell death protein 1; PD-L1, programmed cell death-ligand 1.

Figure 2.

Forest plots illustrating the mean difference in outcomes for different immune checkpoint inhibitor combinations. Forest plots for (A) overall survival, (B) progression-free survival, (C) objective response rate and (D) adverse events are presented. CI, confidence interval; CTLA-4, cytotoxic T-lymphocyte associated protein 4; MD, mean difference; OR, odds ratio; PD-1, programmed cell death protein 1; PD-L1, programmed cell death-ligand 1.

Figure 3.

Pairwise comparisons of overall survival between study arms as reported in individual studies. CTLA-4, cytotoxic T-lymphocyte associated protein 4; OR, odds ratio; PD-1, programmed cell death protein 1; PD-L1, programmed cell death-ligand 1; RCT, randomized control trial.

Figure 4.

Pairwise comparisons of progression-free survival between study arms as reported in individual studies. CTLA-4, cytotoxic T-lymphocyte associated protein 4; MD, mean difference; PD-1, programmed cell death protein 1; PD-L1, programmed cell death-ligand 1; RCT, randomized control trial.

Figure 5.

Pairwise comparisons of objective response rate between study arms as reported in individual studies. CTLA-4, cytotoxic T-lymphocyte associated protein 4; OR, odds ratio; PD-1, programmed cell death protein 1; PD-L1, programmed cell death-ligand 1; RCT, randomized control trial.

Figure 6.

Pairwise comparisons of adverse events between study arms as reported in individual studies. CTLA-4, cytotoxic T-lymphocyte associated protein 4; OR, odds ratio; PD-1, programmed cell death protein 1; PD-L1, programmed cell death-ligand 1; RCT, randomized control trial.