Cited 19 times in
Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 조병철 | - |
dc.date.accessioned | 2024-03-22T05:46:05Z | - |
dc.date.available | 2024-03-22T05:46:05Z | - |
dc.date.issued | 2023-04 | - |
dc.identifier.issn | 0923-7534 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/198194 | - |
dc.description.abstract | Background: We evaluated whether tissue tumor mutational burden (tTMB) and STK11, KEAP1, and KRAS mutations have clinical utility as biomarkers for pembrolizumab monotherapy versus platinum-based chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive (tumor proportion score >1%) advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations in the phase III KEYNOTE-042 trial. Patients and methods: This retrospective exploratory analysis assessed prevalence of tTMB and STK11, KEAP1, and KRAS mutations determined by whole-exome sequencing of tumor tissue and matched normal DNA and their associations with outcomes in KEYNOTE-042. Clinical utility of tTMB was assessed using a prespecified cut point of 175 mutations/exome. Results: Of 793 patients, 345 (43.5%) had tTMB >175 mutations/exome and 448 (56.5%) had tTMB <175 mutations/ exome. No association was observed between PD-L1 expression and tTMB. Continuous tTMB score was associated with improved overall survival (OS) and progression-free survival among patients receiving pembrolizumab (Wald test, one-sided P < 0.001) but not those receiving chemotherapy (Wald test, two-sided P > 0.05). tTMB >175 mutations/exome was associated with improved outcomes for pembrolizumab versus chemotherapy, whereas tTMB <175 mutations/ exome was not {OS: hazard ratio, 0.62 [95% confidence interval (CI) 0.48-0.80] and 1.09 (95% CI 0.88-1.36); progression-free survival: 0.75 (0.59-0.95) and 1.27 (1.04-1.55), respectively}. Improved OS [hazard ratio (95% CI)] for pembrolizumab versus chemotherapy was observed regardless of STK11 [STK11 mutant (n = 33): 0.37 (0.16-0.86), STK11 wild-type (n = 396): 0.83 (0.65-1.05)]; KEAP1 [KEAP1 mutant (n = 64): 0.75 (0.42-1.35), KEAP1 wild-type (n = 365): 0.78 (0.61-0.99)], or KRAS [KRAS mutant (n = 69): 0.42 (0.22-0.81); KRAS wild-type (n = 232): 0.86 (0.63-1.18)] mutation status. Conclusion: tTMB with a cut point of >175 mutations/exome is a potential predictive biomarker for pembrolizumab monotherapy for advanced/metastatic PD-L1 tumor proportion score >1% NSCLC. Pembrolizumab is a standard first-line treatment in this setting regardless of STK11, KEAP1, or KRAS mutation status. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Oxford University Press | - |
dc.relation.isPartOf | ANNALS OF ONCOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Antineoplastic Combined Chemotherapy Protocols / therapeutic use | - |
dc.subject.MESH | B7-H1 Antigen / metabolism | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung* / drug therapy | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung* / genetics | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung* / pathology | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Kelch-Like ECH-Associated Protein 1 / genetics | - |
dc.subject.MESH | Lung Neoplasms* / drug therapy | - |
dc.subject.MESH | Lung Neoplasms* / genetics | - |
dc.subject.MESH | Lung Neoplasms* / pathology | - |
dc.subject.MESH | Mutation | - |
dc.subject.MESH | NF-E2-Related Factor 2 / genetics | - |
dc.subject.MESH | NF-E2-Related Factor 2 / metabolism | - |
dc.subject.MESH | NF-E2-Related Factor 2 / therapeutic use | - |
dc.subject.MESH | Proto-Oncogene Proteins p21(ras) / genetics | - |
dc.subject.MESH | Retrospective Studies | - |
dc.title | Associations of tissue tumor mutational burden and mutational status with clinical outcomes in KEYNOTE-042: pembrolizumab versus chemotherapy for advanced PD-L1-positive NSCLC | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | T S K Mok | - |
dc.contributor.googleauthor | G Lopes | - |
dc.contributor.googleauthor | B C Cho | - |
dc.contributor.googleauthor | D M Kowalski | - |
dc.contributor.googleauthor | K Kasahara | - |
dc.contributor.googleauthor | Y-L Wu | - |
dc.contributor.googleauthor | G de Castro Jr | - |
dc.contributor.googleauthor | H Z Turna | - |
dc.contributor.googleauthor | R Cristescu | - |
dc.contributor.googleauthor | D Aurora-Garg | - |
dc.contributor.googleauthor | A Loboda | - |
dc.contributor.googleauthor | J Lunceford | - |
dc.contributor.googleauthor | J Kobie | - |
dc.contributor.googleauthor | M Ayers | - |
dc.contributor.googleauthor | M C Pietanza | - |
dc.contributor.googleauthor | B Piperdi | - |
dc.contributor.googleauthor | R S Herbst | - |
dc.identifier.doi | 10.1016/j.annonc.2023.01.011 | - |
dc.contributor.localId | A03822 | - |
dc.relation.journalcode | J00171 | - |
dc.identifier.eissn | 1569-8041 | - |
dc.identifier.pmid | 36709038 | - |
dc.subject.keyword | biomarker | - |
dc.subject.keyword | locally advanced or metastatic non-small-cell lung cancer | - |
dc.subject.keyword | pembrolizumab | - |
dc.subject.keyword | single-gene genetic alterations | - |
dc.subject.keyword | tissue tumor mutational burden | - |
dc.contributor.alternativeName | Cho, Byoung Chul | - |
dc.contributor.affiliatedAuthor | 조병철 | - |
dc.citation.volume | 34 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 377 | - |
dc.citation.endPage | 388 | - |
dc.identifier.bibliographicCitation | ANNALS OF ONCOLOGY, Vol.34(4) : 377-388, 2023-04 | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.