Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/130505
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dc.contributor.authorGarassino, Marina C.en_US
dc.contributor.authorGadgeel, Shirishen_US
dc.contributor.authorNovello, Silviaen_US
dc.contributor.authorHalmos, Balazsen_US
dc.contributor.authorFelip, Enriquetaen_US
dc.contributor.authorSperanza, Giovannaen_US
dc.contributor.authorHui, Rinaen_US
dc.contributor.authorGaron, Edward B.en_US
dc.contributor.authorHorinouchi, Hidehitoen_US
dc.contributor.authorSugawara, Shunichien_US
dc.contributor.authorRodríguez Abreu, Delvysen_US
dc.contributor.authorReck, Martinen_US
dc.contributor.authorCristescu, Razvanen_US
dc.contributor.authorAurora-Garg, Deeptien_US
dc.contributor.authorLoboda, Andreyen_US
dc.contributor.authorLunceford, Jareden_US
dc.contributor.authorKobie, Julieen_US
dc.contributor.authorAyers, Marken_US
dc.contributor.authorPiperdi, Bilalen_US
dc.contributor.authorPietanza, M. Catherineen_US
dc.contributor.authorPaz-Ares, Luisen_US
dc.date.accessioned2024-05-17T16:38:50Z-
dc.date.available2024-05-17T16:38:50Z-
dc.date.issued2023en_US
dc.identifier.issn2666-3643en_US
dc.identifier.otherWoS-
dc.identifier.urihttp://hdl.handle.net/10553/130505-
dc.description.abstractIntroduction: We evaluated tissue tumor mutational burden (tTMB) and mutations in STK11, KEAP1, and KRAS as biomarkers for outcomes with pembrolizumab plus platinum-based chemotherapy (pembrolizumab-combination) for NSCLC among patients in the phase 3 KEYNOTE-189 (ClinicalTrials.gov, NCT02578680; nonsquamous) and KEYNOTE-407 (ClinicalTrials.gov, NCT02775435; squamous) trials. Methods: This retrospective exploratory analysis evaluated prevalence of high tTMB and STK11, KEAP1, and KRAS mutations in patients enrolled in KEYNOTE-189 and KEYNOTE-407 and the relationship between these potential biomarkers and clinical outcomes. tTMB and STK11, KEAP1, and KRAS mutation status was assessed using whole-exome sequencing in patients with available tumor and matched normal DNA. The clinical utility of tTMB was assessed using a prespecified cutpoint of 175 mutations/exome. Results: Among patients with evaluable data from whole-exome sequencing for evaluation of tTMB (KEYNOTE-189, n = 293; KEYNOTE-407, n = 312) and matched normal DNA, no association was found between continuous tTMB score and overall survival (OS) or progression-free survival for pembrolizumab-combination (Wald test, one-sided p > 0.05) or placebo-combination (Wald test, two-sided p > 0.05) in patients with squamous or nonsquamous histology. Pembrolizumab-combination improved outcomes for patients with tTMB greater than or equal to 175 compared with tTMB less than 175 mutations/exome in KEYNOTE-189 (OS, hazard ratio = 0.64 [95% confidence interval (CI): 0.38-1.07] and 0.64 [95% CI: 0.42-0.97], respectively) and KEYNOTE-407 (OS, hazard ratio = 0.74 [95% CI: 0.50-1.08 and 0.86 [95% CI: 0.57-1.28], respectively) versus placebo-combination. Treatment outcomes were similar regardless of KEAP1, STK11, or KRAS mutation status. Conclusions: These findings support pembrolizumab-combination as first-line treatment in patients with metastatic NSCLC and do not suggest the utility of tTMB, STK11, KEAP1, or KRAS mutation status as a biomarker for this regimen. (c) 2022 The Authors. Published by Elsevier Inc. on behalf ofthe International Association for the Study of Lung Cancer.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.languageengen_US
dc.relation.ispartofJTO Clinical and Research Reportsen_US
dc.sourceJto Clinical And Research Reports [2666-3643],v. 4 (1), (Enero 2023)en_US
dc.subject32 Ciencias médicasen_US
dc.subject320708 Hematologíaen_US
dc.subject320713 Oncologíaen_US
dc.subject.otherLungen_US
dc.subject.otherBlockadeen_US
dc.subject.otherPatternsen_US
dc.subject.otherImpacten_US
dc.subject.otherKrasen_US
dc.subject.otherTmben_US
dc.subject.otherTissue Tumor Mutational Burdenen_US
dc.subject.otherSingle-Gene Genetic Alterationsen_US
dc.subject.otherPembrolizumaben_US
dc.subject.otherMetastatic Non-Small-Cell Lung Canceren_US
dc.subject.otherBiomarkeren_US
dc.titleAssociations of Tissue Tumor Mutational Burden and Mutational Status With Clinical Outcomes With Pembrolizumab Plus Chemotherapy Versus Chemotherapy For Metastatic NSCLCen_US
dc.typeinfo:eu-repo/semantics/Articleen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.jtocrr.2022.100431en_US
dc.identifier.isi001165404600001-
dc.identifier.eissn2666-3643-
dc.identifier.issue1-
dc.relation.volume4en_US
dc.investigacionCiencias de la Saluden_US
dc.type2Artículoen_US
dc.contributor.daisngid52398171-
dc.contributor.daisngid54285580-
dc.contributor.daisngid1632951-
dc.contributor.daisngid22400739-
dc.contributor.daisngid15314754-
dc.contributor.daisngid55152554-
dc.contributor.daisngid22831853-
dc.contributor.daisngid29184612-
dc.contributor.daisngid15554820-
dc.contributor.daisngid15940962-
dc.contributor.daisngid32265208-
dc.contributor.daisngid13525721-
dc.contributor.daisngid29407603-
dc.contributor.daisngid19025192-
dc.contributor.daisngid25186166-
dc.contributor.daisngid11377433-
dc.contributor.daisngid23620936-
dc.contributor.daisngid4351939-
dc.contributor.daisngid45807733-
dc.contributor.daisngid27478402-
dc.contributor.daisngid26706737-
dc.description.numberofpages13en_US
dc.utils.revisionen_US
dc.contributor.wosstandardWOS:Garassino, MC-
dc.contributor.wosstandardWOS:Gadgeel, S-
dc.contributor.wosstandardWOS:Novello, S-
dc.contributor.wosstandardWOS:Halmos, B-
dc.contributor.wosstandardWOS:Felip, E-
dc.contributor.wosstandardWOS:Speranza, G-
dc.contributor.wosstandardWOS:Hui, RA-
dc.contributor.wosstandardWOS:Garon, EB-
dc.contributor.wosstandardWOS:Horinouchi, H-
dc.contributor.wosstandardWOS:Sugawara, S-
dc.contributor.wosstandardWOS:Rodriguez-Abreu, D-
dc.contributor.wosstandardWOS:Reck, M-
dc.contributor.wosstandardWOS:Cristescu, R-
dc.contributor.wosstandardWOS:Aurora-Garg, D-
dc.contributor.wosstandardWOS:Loboda, A-
dc.contributor.wosstandardWOS:Lunceford, J-
dc.contributor.wosstandardWOS:Kobie, J-
dc.contributor.wosstandardWOS:Ayers, M-
dc.contributor.wosstandardWOS:Piperdi, B-
dc.contributor.wosstandardWOS:Pietanza, MC-
dc.contributor.wosstandardWOS:Paz-Ares, L-
dc.date.coverdateEnero 2023en_US
dc.identifier.ulpgcen_US
dc.contributor.buulpgcBU-MEDen_US
dc.description.sjr1,321
dc.description.sjrqQ1
item.grantfulltextopen-
item.fulltextCon texto completo-
crisitem.author.deptGIR Nanomaterials and Corrosion-
crisitem.author.deptDepartamento de Ciencias Médicas y Quirúrgicas-
crisitem.author.orcid0000-0003-0506-1366-
crisitem.author.parentorgDepartamento de Ingeniería Mecánica-
crisitem.author.fullNameRodríguez Abreu, Delvys-
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