Clinical utility of tumour mutational burden on efficacy of immune checkpoint inhibitors in malignant solid tumours: protocol for a systematic review and meta-analysis

Introduction A major development in solid malignancy treatment is the application of immune checkpoint inhibitors (ICIs), which have produced durable responses and increased survival rates. However, the therapeutic effect of ICIs has great heterogeneity in patients with cancer. We propose a systematic review to evaluate the predictive value of tumour mutation burden (TMB) on efficacy of ICIs. Methods and analysis A systematic literature search will be conducted in the PubMed, OVID, Web of Science, Embase and Cochrane Central Register of Controlled Trials Library databases up to 31 May 2022. We will compare the efficacy of ICIs between TMB high group and TMB low group in terms of the HRs of overall survival (OS) and progression-free survival (PFS), and the OR of the objective response rate/overall response rate (ORR). The HRs of PFS and OS, and the OR of ORR, will be measured by an inverse variance weighted fixed effects model (I-2 <= 50%) or a DerSimonian-Laird random effects model (I-2>50%). In addition, subgroup analysis, sensitivity analysis, heterogeneity analysis and publication bias will be conducted. We plan to conduct a subgroup analysis on age, sex, area, number of patients (high/low TMB), cancer type, tumour size, stage, line of therapy, TMB sequencing method, type of immunotherapy and follow-up period. Ethics and dissemination Ethical approval and informed consent are not needed, as the study will be a literature review and will not involve direct contact with patients or alterations to patient care. This systematic review is anticipated to be finished in December 2023, and the results will be published in a peer-reviewed journal. PROSPERO registration number CRD42021262480.

Automated summary

This study aims to evaluate the predictive value of tumour mutation burden (TMB) in the efficacy of immune checkpoint inhibitors (ICIs). The study will compare the efficacy of ICIs between patients with high TMB and low TMB, and assess their impact on overall survival, progression-free survival, and objective response rate. Subgroup analysis, sensitivity analysis, heterogeneity analysis, and publication bias will also be conducted.