Efficacy and safety of immune checkpoint inhibitors in colorectal cancer: a systematic review and meta-analysis

Jing Jiang,Jinhua Lu,Tianni Zeng,Xianlei Lin,Xiaojie Fang,Zechen Lin,Shengyou Lin,Yazhen Zhong,Nan Wang

doi:10.1007/s00384-021-04028-z

Abstract

Background and objectiveImmune checkpoint inhibitor (ICI) therapies have shown promising prospects in colorectal cancer (CRC) immunotherapy; many clinical trials have been carried out. In this study, we sought to evaluate the efficacy and safety of ICI therapies in CRC by presenting a meta-analysis of relevant studies.MethodsDatabases including PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for studies concerning the efficacy and safety of ICI in colorectal cancer. The reported odds ratio (OR) or weighted mean difference (WMD) with 95% confidence intervals (CIs) of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAEs), and TRAEs ≥ 3 in the included studies were analyzed by fixed effects/random effects models.ResultsThree studies involving 667 patients with colorectal cancer were included in our meta-analysis. No significant difference between the immune checkpoint inhibitor therapies and conventional therapies in OS (WMD = 0.73, 95% CI − 3.09, 4.54; p = 0.71), in ORR (OR = 1.54, 95% CI 0.98, 2.40; p = 0.06), and in DCR (OR = 0.97, 95% CI 0.36, 2.61; p = 0.95). The median PFS of the ICI therapy group was shorter than that of the conventional therapy group (WMD = − 0.10, 95% CI − 0.18, − 0.02; p = 0.02). At the same time, we also could not find a significant difference between the immune checkpoint inhibitor therapies and conventional therapies in TRAEs (OR = 1.56, 95% CI 0.11, 22.09; p = 0.74) and in TRAEs ≥ 3 (OR = 0.94, 95% CI 0.16, 5.65; p = 0.95).ConclusionImmune checkpoint inhibitor therapies could not improve all survival endpoints to advanced or metastatic colorectal cancer patients. Whether immune checkpoint inhibitors should be the first choice of therapies for colorectal cancer patients with undetermined microsatellite status or not able to determine microsatellite status needs more related studies to prove.

Highlights

Colorectal cancer is the fourth most fatal cancer, with approximately 0.9 million annual mortalities
Pembrolizumab (PD-1) 200 mg/3 weeks ivgtt vs mFOLFOX6 or FOLFOX6 plus bevacizumab 5 mg/kg ivgtt d1/2 weeks or mFOLFOX6 plus cetuximab 400 mg/m2 ivgtt over 2 h followed by 250 mg/m2/week ivgtt or FOLFIRI or FOLFIRI plus bevacizumab or FOLFIRI plus cetuximab
There was no significant difference between the outcomes of immune checkpoint inhibitor therapy and conventional therapy (WMD = 0.73, 95% confidence intervals (CIs) − 3.09, 4.54; p = 0.71)

Summary

Introduction

Colorectal cancer is the fourth most fatal cancer, with approximately 0.9 million annual mortalities. Immune checkpoint inhibitor (ICI) therapies have shown promising prospects in colorectal cancer (CRC) immunotherapy; many clinical trials have been carried out. No significant difference between the immune checkpoint inhibitor therapies and conventional therapies in OS (WMD = 0.73, 95% CI − 3.09, 4.54; p = 0.71), in ORR (OR = 1.54, 95% CI 0.98, 2.40; p = 0.06), and in DCR (OR = 0.97, 95% CI 0.36, 2.61; p = 0.95). Conclusion Immune checkpoint inhibitor therapies could not improve all survival endpoints to advanced or metastatic colorectal cancer patients. Whether immune checkpoint inhibitors should be the first choice of therapies for colorectal cancer patients with undetermined microsatellite status or not able to determine microsatellite status needs more related studies to prove

Methods

Results

Conclusion