Abstract
BackgroundThe 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 methodsThe 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).ResultsEight 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.ConclusionsThis 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.
Highlights
Data collected on Medline (PubMed), Scopus, and Cochrane-Library database were collected until 30 September 2020, restricting the search to English-only articles; potential abstracts published on the databases of the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) were retrieved, as well as results from not-yet-published ongoing studies available on the National Institute of Health (NIH) website because they were considered as a source of gray literature
Statistical analysis was carried out using RevMan version 5.3,34 and Comprehensive Meta-analysis version 2.2.064.35 As already described, the outcomes selected to perform meta-analysis comparisons were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) stratified according to the high- or low-tumor mutational burden (TMB) value
We used the standard meta-analytical technique to compare the performance of IO agents versus CT, according to TMB-high or -low for each selected outcome (ORR, PFS, and OS), calculating the logarithm of the hazard ratios (HRs) or the Risk ratios (RRs) and their standard error for all the randomized clinical trials (RCTs) included in the analysis
Summary
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).
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