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dc.contributor.authorGalvano, A
dc.contributor.authorGristina, V
dc.contributor.authorMalapelle, U
dc.contributor.authorPisapia, P
dc.contributor.authorPepe, F
dc.contributor.authorBarraco, N
dc.contributor.authorCastiglia, M
dc.contributor.authorPerez, A
dc.contributor.authorRolfo, C
dc.contributor.authorTroncone, G
dc.contributor.authorRusso, A
dc.contributor.authorBazan, V
dc.date.accessioned2021-05-05T17:35:12Z
dc.date.available2021-05-05T17:35:12Z
dc.date.issued2021-04-30
dc.identifier.urihttp://hdl.handle.net/10713/15583
dc.description.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.en_US
dc.description.urihttps://doi.org/10.1016/j.esmoop.2021.100124en_US
dc.language.isoenen_US
dc.publisherElsevier Ltd.en_US
dc.relation.ispartofESMO Openen_US
dc.rightsCopyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.en_US
dc.subjectICIsen_US
dc.subjectNSCLCen_US
dc.subjectTMBen_US
dc.subjectmeta-analysisen_US
dc.subjectprognosticen_US
dc.titleThe 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 trialsen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.esmoop.2021.100124
dc.identifier.pmid33940346
dc.source.volume6
dc.source.issue3
dc.source.beginpage100124
dc.source.endpage
dc.source.countryEngland


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