The prognostic impact of tumor mutational burden (TMB) in the first-line management of advanced non-oncogene addicted non-small-cell lung cancer (NSCLC): a systematic review and meta-analysis of randomized controlled trials
MetadataShow full item record
AbstractBACKGROUND: The role of tumor mutational burden (TMB) is still debated for selecting advanced non-oncogene addicted non-small-cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs). Of note, TMB failed to predict a benefit in overall survival (OS) among such patients. MATERIALS AND METHODS: The purpose of this meta-analysis was to compare efficacy outcomes among first-line immune-oncology (IO) agents versus standard platinum-based chemotherapy (CT) within two subgroups (TMB-low and TMB-high on either tissue or blood). We collected hazard ratios (HRs) to evaluate the association for progression-free survival (PFS) and OS, with the relative 95% confidence intervals (CIs). Risk ratios (RRs) were used as an association measure for objective response rate (ORR). RESULTS: Eight different cohorts of five randomized controlled phase III studies (3848 patients) were analyzed. In TMB-high patients, IO agents were associated with improved ORR (RRs 1.37, 95% CI 1.13-1.66), PFS (HR 0.69, 95% CI 0.61-0.79) and OS (HR 0.67, 95% CI 0.59-0.77) when compared with CT, thus suggesting a possible predictive role of high TMB for IO regimens. In TMB-low patients, the IO strategy did not lead to any significant benefit in survival and activity, whereas the pooled results of both ORR and PFS were intriguingly associated with a statistical significance in favor of CT. CONCLUSIONS: This meta-analysis resulted in a proven benefit in OS in favor of IO agents in the TMB-high population. Although more prospective data are warranted, we postulated the hypothesis that monitoring TMB, in addition to the existing programmed death-ligand 1 (PD-L1) expression level, could represent the preferable option for future clinical research in the first-line management of advanced non-oncogene addicted NSCLC patients.
Rights/TermsCopyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/15583
- Association of Survival and Immune-Related Biomarkers With Immunotherapy in Patients With Non-Small Cell Lung Cancer: A Meta-analysis and Individual Patient-Level Analysis.
- Authors: Yu Y, Zeng D, Ou Q, Liu S, Li A, Chen Y, Lin D, Gao Q, Zhou H, Liao W, Yao H
- Issue date: 2019 Jul 3
- Comparison of Efficacy and Safety of Single and Double Immune Checkpoint Inhibitor-Based First-Line Treatments for Advanced Driver-Gene Wild-Type Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.
- Authors: Xu Q, Zhang X, Huang M, Dai X, Gao J, Li S, Sheng L, Huang K, Wang J, Liu L
- Issue date: 2021
- The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis.
- Authors: Ba H, Liu L, Peng Q, Chen J, Zhu YD
- Issue date: 2021 Nov 13
- Predictive value of tumor mutational burden for immunotherapy in non-small cell lung cancer: A systematic review and meta-analysis.
- Authors: Meng G, Liu X, Ma T, Lv D, Sun G
- Issue date: 2022
- Predictive Efficacy of Blood-Based Tumor Mutation Burden Assay for Immune Checkpoint Inhibitors Therapy in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.
- Authors: Zhang N, Zhang J, Wang G, He X, Mi Y, Cao Y, Yu X
- Issue date: 2022