Abstract

ObjectivesFor colorectal cancer patients, traditional biomarker deficient mismatch repair/microsatellite instability (dMMR/MSI) is an accurate predictor of immune checkpoint inhibitors (ICIs). Recent years, researchers considered tumor mutation burden (TMB) as another predictive biomarker which means the number of nonsynonymous mutations in cancer cells. Several studies have proven that TMB can evaluate the efficacy of ICI therapy in diverse types of cancer, especially in non-small cell lung cancer and melanoma. However, studies on the association between TMB and the response to ICI therapy in colorectal cancer alone are still lacking. In this study, we aim to verify the effect of TMB as a biomarker in predicting the efficacy of ICIs in colorectal cancer.MethodsWe searched the PubMed and Ovid MEDLINE databases up to May 1, 2021 and screened studies for eligibility. Thirteen studies published from 2015 to 2021 with 5062 patients were included finally. We extracted and calculated hazard ratios (HRs) and odds ratios (ORs) of overall survival (OS) and objective response rates (ORRs) and their 95% confidence intervals (95% CIs). Pooled HR and OR were evaluated to compare OS and ORR between TMB-high and TMB-low groups in colorectal cancer patients. Meanwhile, we assessed heterogeneity with the I 2 statistic and p-values and performed publication bias assessments, sensitivity analyses, and subgroup analyses to search the cause of heterogeneity.ResultsThe TMB-high patient group had a longer OS than the TMB-low patient group (HR = 0.68, 95% CI: 0.51, 0.92, p = 0.013) among colorectal cancer patients receiving ICIs. In addition, the TMB-high patient group was superior in terms of ORR (OR = 19.25, 95% CI: 10.06, 36.82, p < 0.001) compared to the TMB-low patient group.ConclusionsIn conclusion, this meta-analysis revealed that TMB can be used as a potential predictive biomarker of colorectal cancer patients receiving ICI therapy. Nevertheless, this finding is not stable enough. Therefore, many more randomized controlled trials are needed to prove that TMB is reliable enough to be used clinically to predict the efficacy of immunotherapy in colorectal cancer. And the most relevant biomarker remains to be determined when TMB high overlaps with other biomarkers like MSI and TILs.

Highlights

  • Colorectal cancer (CRC) is a common intestinal malignancy

  • Under a random-effects model, the summary hazard ratio (HR) of overall survival (OS) between the high and low TMB patient groups and the corresponding 95% confidence interval (95% CI) were calculated based on 10 studies including 3849 patients [9, 24, 28,29,30,31,32,33, 36, 37]

  • The results suggested that the OS of TMB-high patient group was longer than that of the TMB-low patient group (HR = 0.68, 95% CI: 0.51, 0.92, p = 0.013; Figure 2)

Read more

Summary

Introduction

On the basis of the Global Cancer Epidemiological Statistics (GLOBOCAN2020) released by World Health Organization, it is estimated that in 2020, the number of new cases and deaths of colorectal cancer ranked second and third among all malignant tumors, respectively [1]. A number of studies have shown that the status of deficient mismatch repair (dMMR)/microsatellite instability (MSI) can be used as a biomarker to identify patients who may benefit from immunotherapy [3,4,5]. Only 5% of patients with mCRC are dMMR/MSI-High and some of them do not respond to immunotherapy, which has limited clinical benefits. It is necessary to look for more effective biomarkers to expand the CRC population responding to immunotherapy

Objectives
Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call