Associations of Tissue Tumor Mutational Burden and Mutational Status With Clinical Outcomes With Pembrolizumab Plus Chemotherapy Versus Chemotherapy For Metastatic NSCLC
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...
Gespeichert in:
| Veröffentlicht in: | JTO clinical and research reports Jg. 4; H. 1; S. 100431 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
United States
Elsevier Inc
01.01.2023
Elsevier |
| Schlagworte: | |
| ISSN: | 2666-3643, 2666-3643 |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Abstract | 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.
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.
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.
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. |
|---|---|
| AbstractList | 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.
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.
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.
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. We evaluated tissue tumor mutational burden (tTMB) and mutations in and 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. This retrospective exploratory analysis evaluated prevalence of high tTMB and , and mutations in patients enrolled in KEYNOTE-189 and KEYNOTE-407 and the relationship between these potential biomarkers and clinical outcomes. tTMB and , , and 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. Among patients with evaluable data from whole-exome sequencing for evaluation of tTMB (KEYNOTE-189, = 293; KEYNOTE-407, = 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 > 0.05) or placebo-combination (Wald test, two-sided > 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 , or mutation status. These findings support pembrolizumab-combination as first-line treatment in patients with metastatic NSCLC and do not suggest the utility of tTMB, or mutation status as a biomarker for this regimen. 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.IntroductionWe 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.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.MethodsThis 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.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.ResultsAmong 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.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.ConclusionsThese 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. Introduction: 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. AbstractIntroductionWe 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. MethodsThis 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 use of tTMB was assessed using a prespecified cutpoint of 175 mutations/exome. ResultsAmong patients with assessable 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. ConclusionsThese findings support pembrolizumab-combination as first-line treatment in patients with metastatic NSCLC and do not suggest the use of tTMB, STK11, KEAP1, or KRAS mutation status as a biomarker for this regimen. |
| ArticleNumber | 100431 |
| Author | Garassino, Marina C. Garon, Edward B. Loboda, Andrey Reck, Martin Paz-Ares, Luis Cristescu, Razvan Felip, Enriqueta Rodriguez-Abreu, Delvys Hui, Rina Halmos, Balazs Pietanza, M. Catherine Horinouchi, Hidehito Novello, Silvia Speranza, Giovanna Sugawara, Shunichi Lunceford, Jared Aurora-Garg, Deepti Piperdi, Bilal Ayers, Mark Gadgeel, Shirish Kobie, Julie |
| Author_xml | – sequence: 1 givenname: Marina C. surname: Garassino fullname: Garassino, Marina C. email: mgarassino@medicine.bsd.uchicago.edu organization: Section of Hematology/Oncology, Thoracic Oncology program, University of Chicago, Chicago, Illinois, and IRCCS Istituto Nazionale dei Tumori, Milano – sequence: 2 givenname: Shirish surname: Gadgeel fullname: Gadgeel, Shirish organization: Division of Hematology/Oncology, Department of Internal Medicine, Henry Ford Cancer Institute/Henry Ford Health System, Detroit, Michigan – sequence: 3 givenname: Silvia surname: Novello fullname: Novello, Silvia organization: Department of Oncology, University of Turin, Orbassano, Italy – sequence: 4 givenname: Balazs surname: Halmos fullname: Halmos, Balazs organization: Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York – sequence: 5 givenname: Enriqueta surname: Felip fullname: Felip, Enriqueta organization: Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University, Barcelona, Spain – sequence: 6 givenname: Giovanna surname: Speranza fullname: Speranza, Giovanna organization: Centre integré de cancérologie de la Montérégie, Université de Sherbrooke, Greenfield Park, Quebec, Canada – sequence: 7 givenname: Rina surname: Hui fullname: Hui, Rina organization: Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia – sequence: 8 givenname: Edward B. surname: Garon fullname: Garon, Edward B. organization: David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California – sequence: 9 givenname: Hidehito surname: Horinouchi fullname: Horinouchi, Hidehito organization: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan – sequence: 10 givenname: Shunichi surname: Sugawara fullname: Sugawara, Shunichi organization: Department of Pulmonary Medicine, Sendai Kousei Hospital, Miyagi, Japan – sequence: 11 givenname: Delvys surname: Rodriguez-Abreu fullname: Rodriguez-Abreu, Delvys organization: Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain – sequence: 12 givenname: Martin surname: Reck fullname: Reck, Martin organization: LungenClinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany – sequence: 13 givenname: Razvan surname: Cristescu fullname: Cristescu, Razvan organization: Merck & Co., Inc., Rahway, New Jersey – sequence: 14 givenname: Deepti surname: Aurora-Garg fullname: Aurora-Garg, Deepti organization: Merck & Co., Inc., Rahway, New Jersey – sequence: 15 givenname: Andrey surname: Loboda fullname: Loboda, Andrey organization: Merck & Co., Inc., Rahway, New Jersey – sequence: 16 givenname: Jared surname: Lunceford fullname: Lunceford, Jared organization: Merck & Co., Inc., Rahway, New Jersey – sequence: 17 givenname: Julie surname: Kobie fullname: Kobie, Julie organization: Merck & Co., Inc., Rahway, New Jersey – sequence: 18 givenname: Mark surname: Ayers fullname: Ayers, Mark organization: Merck & Co., Inc., Rahway, New Jersey – sequence: 19 givenname: Bilal surname: Piperdi fullname: Piperdi, Bilal organization: Merck & Co., Inc., Rahway, New Jersey – sequence: 20 givenname: M. Catherine surname: Pietanza fullname: Pietanza, M. Catherine organization: Merck & Co., Inc., Rahway, New Jersey – sequence: 21 givenname: Luis surname: Paz-Ares fullname: Paz-Ares, Luis organization: Hospital Universitario 12 de Octubre, Spanish National Cancer Research Center, Universidad Complutense and Ciberonc, Madrid, Spain |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36793385$$D View this record in MEDLINE/PubMed |
| BookMark | eNqVUttu1DAQjVARLaV_gFAeednFl1xshJBKRKHSQivtAo-W1550HZJ4ayeVlj_iL3GaFG0roYonW2fmnDOaOc-jg9a2EEUvMZpjhLM31bzqrHJuThAhAUIJxU-iI5Jl2YxmCT3Y-x9GJ95XCCGSYpwz8iw6pFnOKWXpUfT71HurjOyMbX1sy3hlvO8hXvWNdfGXvrutyDr-0DsNbSxbvY8uw6_38Q_TbeKiNq1RAbzoO2UbmOBLaNbO1uZX38h1fFmH9mIDje024OR2F38H5x9iZ4M3dNIPRir-uiwWxYvoaSlrDyfTexx9O_u4Kj7PFhefzovTxUxlNO9mTEudYk05B8xKjnKNtcRIUslohrReqzLTeYlylqQlUyxRGEGesBIFIgNKj6PzUVdbWYmtM410O2GlEbeAdVdCujBVDSJdUxwYUrJMJjhhnFPQvFSSA8epVEHr_ai17dcNaAVt52R9T_R-pTUbcWVvBOeEYj4M83oScPa6B9-JxngFdS1bsL0XJM_zBKUpTkPrq32vvyZ3tw4Nb8cG5az3DkqhzHjIYG1qgZEYsiUqMWZLDNkSY7YCOXlAvtN_hDYtAMLFbgw44ZWBVoE2DlQXVmr-V0BNMfsJO_CV7V3IoRdYeCKQWA6pH0JPCEI4TUkQePdvgcf9_wBjXBgv |
| CitedBy_id | crossref_primary_10_3389_fonc_2023_1249237 crossref_primary_10_1080_21645515_2024_2429893 crossref_primary_10_1007_s11523_022_00937_3 crossref_primary_10_1007_s10555_025_10272_4 crossref_primary_10_1136_jitc_2022_005801 |
| Cites_doi | 10.1016/j.jtho.2016.11.343 10.1016/j.esmoop.2021.100124 10.1056/NEJMc1713444 10.1038/ng.3564 10.1200/JCO.18.00149 10.1002/gcc.22733 10.1056/NEJMoa1801946 10.1016/S0140-6736(18)32409-7 10.1093/annonc/mdy474 10.1126/science.aar3593 10.1056/NEJMoa1810865 10.1136/esmoopen-2020-000706 10.1016/S1470-2045(20)30445-9 10.1038/s41588-018-0312-8 10.1001/jamaoncol.2020.0237 10.1126/science.aaa1348 10.1093/annonc/mdz394.077 10.1158/1538-7445.AM2020-CT084 10.1016/j.lungcan.2019.05.015 10.1038/s41568-019-0179-8 10.21037/jtd.2018.11.102 10.1016/j.ccell.2018.03.018 10.1093/annonc/mdw436 10.1172/JCI91190 10.1056/NEJMoa1606774 10.1158/1538-7445.AM2019-SY42-02 10.1056/NEJMoa1613493 10.1016/j.cmet.2018.02.006 10.1158/1078-0432.CCR-19-3663 10.1200/JCO.2017.75.3384 10.1056/NEJMoa1801005 10.1186/s40425-019-0647-4 10.1038/nature13385 10.1038/s41588-018-0200-2 10.1172/jci.insight.126908 10.1200/JCO.18.01042 10.1016/j.lungcan.2019.01.003 |
| ContentType | Journal Article |
| Copyright | 2022 The Authors 2022 The Authors. 2022 The Authors 2022 |
| Copyright_xml | – notice: 2022 The Authors – notice: 2022 The Authors. – notice: 2022 The Authors 2022 |
| DBID | 6I. AAFTH AAYXX CITATION NPM 7X8 5PM DOA |
| DOI | 10.1016/j.jtocrr.2022.100431 |
| DatabaseName | ScienceDirect Open Access Titles Elsevier:ScienceDirect:Open Access CrossRef PubMed MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals |
| DatabaseTitle | CrossRef PubMed MEDLINE - Academic |
| DatabaseTitleList | PubMed MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 2666-3643 |
| EndPage | 100431 |
| ExternalDocumentID | oai_doaj_org_article_5b31e33aa86a4148993ed9fca9e915ac PMC9923193 36793385 10_1016_j_jtocrr_2022_100431 S2666364322001552 1_s2_0_S2666364322001552 |
| Genre | Journal Article |
| GrantInformation_xml | – fundername: NCI NIH HHS grantid: P30 CA016042 |
| GroupedDBID | .1- .FO 0R~ 1P~ 53G AAEDW AALRI AAXUO AAYWO ACVFH ADCNI ADVLN AEUPX AFJKZ AFPUW AFRHN AIGII AITUG AJUYK AKBMS AKYEP ALMA_UNASSIGNED_HOLDINGS AMRAJ APXCP EBS FDB GROUPED_DOAJ M41 M~E OK1 ROL RPM Z5R AAHOK AFCTW NCXOZ 6I. AAFTH AAYXX CITATION NPM 7X8 5PM |
| ID | FETCH-LOGICAL-c637t-8dad51d399e18f907d1da10a3a8360ddbcf6d7f07845f8c84c10e748f0dad8e33 |
| IEDL.DBID | DOA |
| ISICitedReferencesCount | 41 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=001165404600001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 2666-3643 |
| IngestDate | Fri Oct 03 12:45:48 EDT 2025 Thu Aug 21 18:38:18 EDT 2025 Fri Sep 05 10:42:38 EDT 2025 Thu Oct 16 01:42:14 EDT 2025 Tue Nov 18 21:55:42 EST 2025 Thu Nov 20 00:42:45 EST 2025 Tue Jul 25 20:56:40 EDT 2023 Tue Feb 25 19:54:55 EST 2025 Tue Aug 26 19:33:20 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 1 |
| Keywords | Pembrolizumab Biomarker Tissue tumor mutational burden Single-gene genetic alterations Metastatic non‒small-cell lung cancer |
| Language | English |
| License | This is an open access article under the CC BY-NC-ND license. 2022 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c637t-8dad51d399e18f907d1da10a3a8360ddbcf6d7f07845f8c84c10e748f0dad8e33 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | https://doaj.org/article/5b31e33aa86a4148993ed9fca9e915ac |
| PMID | 36793385 |
| PQID | 2777405515 |
| PQPubID | 23479 |
| PageCount | 1 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_5b31e33aa86a4148993ed9fca9e915ac pubmedcentral_primary_oai_pubmedcentral_nih_gov_9923193 proquest_miscellaneous_2777405515 pubmed_primary_36793385 crossref_citationtrail_10_1016_j_jtocrr_2022_100431 crossref_primary_10_1016_j_jtocrr_2022_100431 elsevier_sciencedirect_doi_10_1016_j_jtocrr_2022_100431 elsevier_clinicalkeyesjournals_1_s2_0_S2666364322001552 elsevier_clinicalkey_doi_10_1016_j_jtocrr_2022_100431 |
| PublicationCentury | 2000 |
| PublicationDate | 2023-01-01 |
| PublicationDateYYYYMMDD | 2023-01-01 |
| PublicationDate_xml | – month: 01 year: 2023 text: 2023-01-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | JTO clinical and research reports |
| PublicationTitleAlternate | JTO Clin Res Rep |
| PublicationYear | 2023 |
| Publisher | Elsevier Inc Elsevier |
| Publisher_xml | – name: Elsevier Inc – name: Elsevier |
| References | Cristescu, Mogg, Ayers (bib22) 2018; 362 Merino, McShane, Fabrizio (bib23) 2020; 8 Ayers, Lunceford, Nebozhyn (bib24) 2017; 127 Marabelle, Fakih, Lopez (bib26) 2020; 21 Aredo, Padda, Kunder (bib19) 2019; 133 Cho, Lopes, Kowalski (bib41) 2020; 80 La Fleur, Falk-Sorqvist, Smeds (bib18) 2019; 130 Herbst, Lopes, Kowalski (bib30) 2019; 30 Aurora-Garg D, Albright A, Qiu P, et al. Large-scale evaluation of concordance of genomic scores in whole exome sequencing and Foundation Medicine comprehensive genomic platform across cancer types. Paper presented at: Society for Immunotherapy of Cancer (SITC); November 6–10, 2019. National Harbor, MD. Reck, Rodriguez-Abreu, Robinson (bib35) 2019; 37 Hellmann, Ciuleanu, Pluzanski (bib11) 2018; 378 Campbell, Alexandrov, Kim (bib15) 2016; 48 Rizvi, Cho, Reinmuth (bib32) 2020; 6 Ready, Hellmann, Awad (bib13) 2019; 37 Panda, Betigeri, Subramanian (bib25) 2017; 2017 Reck, Rodriguez-Abreu, Robinson (bib34) 2016; 375 (bib16) 2014; 511 Kadara, Choi, Zhang (bib21) 2017; 28 Rizvi, Sanchez-Vega, La (bib39) 2018; 36 Stenzinger, Allen, Maas (bib6) 2019; 58 Miao, Margolis, Vokes (bib40) 2018; 50 Aggarwal, Thompson, Chien (bib37) 2020; 26 Fancello, Gandini, Pelicci, Mazzarella (bib5) 2019; 7 Yarchoan, Albacker, Hopkins (bib7) 2019; 4 Galvano, Gristina, Malapelle (bib8) 2021; 6 Skoulidis, Heymach (bib17) 2019; 19 Skoulidis (bib38) 2019; 79 Samstein, Lee, Shoushtari (bib42) 2019; 51 Rizvi, Hellmann, Snyder (bib9) 2015; 348 Kowanetz, Zou, Shames (bib12) 2017; 12 Papillon-Cavanagh, Doshi, Dobrin, Szustakowski, Walsh (bib29) 2020; 5 Yarchoan, Hopkins, Jaffee (bib33) 2017; 377 Cristescu, Aurora-Garg, Albright (bib28) 2022; 10 Planchard, Popat, Kerr (bib2) 2019; 30 Best, De Souza, Kersbergen (bib20) 2018; 27 Paz-Ares, Luft, Vicente (bib4) 2018; 379 Hellmann, Nathanson, Rizvi (bib31) 2018; 33 bib1 Berland, Heeke, Humbert (bib10) 2019; 11 Carbone, Reck, Paz-Ares (bib14) 2017; 376 Gandhi, Rodriguez-Abreu, Gadgeel (bib3) 2018; 378 Mok, Wu, Kudaba (bib36) 2019; 393 Aggarwal (10.1016/j.jtocrr.2022.100431_bib37) 2020; 26 Mok (10.1016/j.jtocrr.2022.100431_bib36) 2019; 393 Gandhi (10.1016/j.jtocrr.2022.100431_bib3) 2018; 378 Panda (10.1016/j.jtocrr.2022.100431_bib25) 2017; 2017 Yarchoan (10.1016/j.jtocrr.2022.100431_bib33) 2017; 377 Rizvi (10.1016/j.jtocrr.2022.100431_bib39) 2018; 36 (10.1016/j.jtocrr.2022.100431_bib16) 2014; 511 Best (10.1016/j.jtocrr.2022.100431_bib20) 2018; 27 Galvano (10.1016/j.jtocrr.2022.100431_bib8) 2021; 6 Paz-Ares (10.1016/j.jtocrr.2022.100431_bib4) 2018; 379 Kowanetz (10.1016/j.jtocrr.2022.100431_bib12) 2017; 12 Reck (10.1016/j.jtocrr.2022.100431_bib35) 2019; 37 Skoulidis (10.1016/j.jtocrr.2022.100431_bib17) 2019; 19 Carbone (10.1016/j.jtocrr.2022.100431_bib14) 2017; 376 Campbell (10.1016/j.jtocrr.2022.100431_bib15) 2016; 48 Berland (10.1016/j.jtocrr.2022.100431_bib10) 2019; 11 Rizvi (10.1016/j.jtocrr.2022.100431_bib32) 2020; 6 Aredo (10.1016/j.jtocrr.2022.100431_bib19) 2019; 133 Merino (10.1016/j.jtocrr.2022.100431_bib23) 2020; 8 Fancello (10.1016/j.jtocrr.2022.100431_bib5) 2019; 7 Ayers (10.1016/j.jtocrr.2022.100431_bib24) 2017; 127 Kadara (10.1016/j.jtocrr.2022.100431_bib21) 2017; 28 Planchard (10.1016/j.jtocrr.2022.100431_bib2) 2019; 30 Skoulidis (10.1016/j.jtocrr.2022.100431_bib38) 2019; 79 Rizvi (10.1016/j.jtocrr.2022.100431_bib9) 2015; 348 10.1016/j.jtocrr.2022.100431_bib27 Hellmann (10.1016/j.jtocrr.2022.100431_bib31) 2018; 33 Stenzinger (10.1016/j.jtocrr.2022.100431_bib6) 2019; 58 Reck (10.1016/j.jtocrr.2022.100431_bib34) 2016; 375 Cho (10.1016/j.jtocrr.2022.100431_bib41) 2020; 80 Herbst (10.1016/j.jtocrr.2022.100431_bib30) 2019; 30 Hellmann (10.1016/j.jtocrr.2022.100431_bib11) 2018; 378 Papillon-Cavanagh (10.1016/j.jtocrr.2022.100431_bib29) 2020; 5 Miao (10.1016/j.jtocrr.2022.100431_bib40) 2018; 50 Cristescu (10.1016/j.jtocrr.2022.100431_bib28) 2022; 10 Yarchoan (10.1016/j.jtocrr.2022.100431_bib7) 2019; 4 Ready (10.1016/j.jtocrr.2022.100431_bib13) 2019; 37 La Fleur (10.1016/j.jtocrr.2022.100431_bib18) 2019; 130 Cristescu (10.1016/j.jtocrr.2022.100431_bib22) 2018; 362 Marabelle (10.1016/j.jtocrr.2022.100431_bib26) 2020; 21 Samstein (10.1016/j.jtocrr.2022.100431_bib42) 2019; 51 41089738 - JTO Clin Res Rep. 2025 Sep 02;6(10):100892. doi: 10.1016/j.jtocrr.2025.100892. |
| References_xml | – volume: 6 year: 2021 ident: bib8 article-title: 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 publication-title: ESMO Open – volume: 21 start-page: 1353 year: 2020 end-page: 1365 ident: bib26 article-title: Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study publication-title: Lancet Oncol – volume: 375 start-page: 1823 year: 2016 end-page: 1833 ident: bib34 article-title: Pembrolizumab versus chemotherapy for PD-L1-positive non–small-cell lung cancer publication-title: N Engl J Med – volume: 30 start-page: v916 year: 2019 end-page: v917 ident: bib30 article-title: Association between tissue TMB (tTMB) and clinical outcomes with pembrolizumab monotherapy (pembro) in PD-L1-positive advanced NSCLC in the KEYNOTE-010 and −042 trials publication-title: Ann Oncol – volume: 7 start-page: 183 year: 2019 ident: bib5 article-title: Tumor mutational burden quantification from targeted gene panels: major advancements and challenges publication-title: J Immunother Cancer – volume: 4 year: 2019 ident: bib7 article-title: PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers publication-title: JCI Insight – volume: 37 start-page: 537 year: 2019 end-page: 546 ident: bib35 article-title: Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater publication-title: J Clin Oncol – volume: 130 start-page: 50 year: 2019 end-page: 58 ident: bib18 article-title: Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11 publication-title: Lung Cancer – volume: 378 start-page: 2093 year: 2018 end-page: 2104 ident: bib11 article-title: Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden publication-title: N Engl J Med – volume: 10 year: 2022 ident: bib28 article-title: Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors publication-title: J Immunother Cancer – volume: 11 start-page: S71 year: 2019 end-page: S80 ident: bib10 article-title: Current views on tumor mutational burden in patients with non-small cell lung cancer treated by immune checkpoint inhibitors publication-title: J Thorac Dis – volume: 379 start-page: 2040 year: 2018 end-page: 2051 ident: bib4 article-title: Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer publication-title: N Engl J Med – volume: 393 start-page: 1819 year: 2019 end-page: 1830 ident: bib36 article-title: Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial publication-title: Lancet – volume: 376 start-page: 2415 year: 2017 end-page: 2426 ident: bib14 article-title: First-line nivolumab in stage IV or recurrent non-small-cell lung cancer publication-title: N Engl J Med – volume: 8 year: 2020 ident: bib23 article-title: Establishing guidelines to harmonize tumor mutational burden (TMB): in silico assessment of variation in TMB quantification across diagnostic platforms: phase I of the Friends of Cancer Research TMB Harmonization Project publication-title: J Immunother Cancer – volume: 12 start-page: S321 year: 2017 end-page: S322 ident: bib12 article-title: Tumor mutation burden (TMB) is associated with improved efficacy of atezolizumab in 1l and 2l+ NSCLC patients publication-title: J Thorac Oncol – volume: 27 start-page: 935 year: 2018 end-page: 943.e4 ident: bib20 article-title: Synergy between the KEAP1/NRF2 and PI3K pathways drives non-small-cell lung cancer with an altered immune microenvironment publication-title: Cell Metab – volume: 37 start-page: 992 year: 2019 end-page: 1000 ident: bib13 article-title: First-line nivolumab plus ipilimumab in advanced non-small-cell lung cancer (CheckMate 568): outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers publication-title: J Clin Oncol – volume: 127 start-page: 2930 year: 2017 end-page: 2940 ident: bib24 article-title: IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade publication-title: J Clin Invest – volume: 50 start-page: 1271 year: 2018 end-page: 1281 ident: bib40 article-title: Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors publication-title: Nat Genet – volume: 33 start-page: 843 year: 2018 end-page: 852 ident: bib31 article-title: Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer publication-title: Cancer Cell – volume: 48 start-page: 607 year: 2016 end-page: 616 ident: bib15 article-title: Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas publication-title: Nat Genet – volume: 133 start-page: 144 year: 2019 end-page: 150 ident: bib19 article-title: Impact of KRAS mutation subtype and concurrent pathogenic mutations on non-small cell lung cancer outcomes publication-title: Lung Cancer – volume: 28 start-page: 75 year: 2017 end-page: 82 ident: bib21 article-title: Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up publication-title: Ann Oncol – volume: 378 start-page: 2078 year: 2018 end-page: 2092 ident: bib3 article-title: Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer publication-title: N Engl J Med – volume: 377 start-page: 2500 year: 2017 end-page: 2501 ident: bib33 article-title: Tumor mutational burden and response rate to PD-1 inhibition publication-title: N Engl J Med – volume: 26 start-page: 2354 year: 2020 end-page: 2361 ident: bib37 article-title: Baseline plasma tumor mutation burden predicts response to pembrolizumab-based therapy in patients with metastatic non-small cell lung cancer publication-title: Clin Cancer Res – volume: 51 start-page: 202 year: 2019 end-page: 206 ident: bib42 article-title: Tumor mutational load predicts survival after immunotherapy across multiple cancer types publication-title: Nat Genet – ident: bib1 article-title: NCCN clinical practice guidelines in oncology [NCCN Guidelines]: non-small-cell lung cancer, version 3.2019 – volume: 6 start-page: 661 year: 2020 end-page: 674 ident: bib32 article-title: Durvalumab with or without tremelimumab vs standard chemotherapy in first-line treatment of metastatic non-small cell lung cancer: the MYSTIC Phase 3 randomized clinical trial publication-title: JAMA Oncol – volume: 362 start-page: eaar3593 year: 2018 ident: bib22 article-title: Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy publication-title: Science – volume: 19 start-page: 495 year: 2019 end-page: 509 ident: bib17 article-title: Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy publication-title: Nat Rev Cancer – volume: 5 year: 2020 ident: bib29 article-title: STK11 and KEAP1 mutations as prognostic biomarkers in an observational real-world lung adenocarcinoma cohort publication-title: ESMO Open – volume: 348 start-page: 124 year: 2015 end-page: 128 ident: bib9 article-title: Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer publication-title: Science – volume: 58 start-page: 578 year: 2019 end-page: 588 ident: bib6 article-title: Tumor mutational burden standardization initiatives: recommendations for consistent tumor mutational burden assessment in clinical samples to guide immunotherapy treatment decisions publication-title: Genes Chromosomes Cancer – reference: Aurora-Garg D, Albright A, Qiu P, et al. Large-scale evaluation of concordance of genomic scores in whole exome sequencing and Foundation Medicine comprehensive genomic platform across cancer types. Paper presented at: Society for Immunotherapy of Cancer (SITC); November 6–10, 2019. National Harbor, MD. – volume: 2017 year: 2017 ident: bib25 article-title: Identifying a clinically applicable mutational burden threshold as a potential biomarker of response to immune checkpoint therapy in solid tumors publication-title: JCO Precis Oncol – volume: 511 start-page: 543 year: 2014 end-page: 550 ident: bib16 article-title: Comprehensive molecular profiling of lung adenocarcinoma publication-title: Nature – volume: 36 start-page: 633 year: 2018 end-page: 641 ident: bib39 article-title: Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing publication-title: J Clin Oncol – volume: 79 year: 2019 ident: bib38 article-title: Inactivating STK11/LKB1 genomic alterations are a major driver of primary resistance to PD-1 axis blockade in non-squamous non-small cell lung cancer publication-title: Cancer Res – volume: 80 start-page: CT084 year: 2020 ident: bib41 article-title: Relationship between STK11 and KEAP1 mutational status and efficacy in KEYNOTE-042: pembrolizumab monotherapy versus platinum-based chemotherapy as first-line therapy for PD-L1-positive advanced NSCLC publication-title: Cancer Res – volume: 30 start-page: 863 year: 2019 end-page: 870 ident: bib2 article-title: Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up publication-title: Ann Oncol – volume: 12 start-page: S321 issue: suppl year: 2017 ident: 10.1016/j.jtocrr.2022.100431_bib12 article-title: Tumor mutation burden (TMB) is associated with improved efficacy of atezolizumab in 1l and 2l+ NSCLC patients publication-title: J Thorac Oncol doi: 10.1016/j.jtho.2016.11.343 – volume: 6 year: 2021 ident: 10.1016/j.jtocrr.2022.100431_bib8 article-title: 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 publication-title: ESMO Open doi: 10.1016/j.esmoop.2021.100124 – volume: 377 start-page: 2500 year: 2017 ident: 10.1016/j.jtocrr.2022.100431_bib33 article-title: Tumor mutational burden and response rate to PD-1 inhibition publication-title: N Engl J Med doi: 10.1056/NEJMc1713444 – volume: 48 start-page: 607 year: 2016 ident: 10.1016/j.jtocrr.2022.100431_bib15 article-title: Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas publication-title: Nat Genet doi: 10.1038/ng.3564 – volume: 2017 year: 2017 ident: 10.1016/j.jtocrr.2022.100431_bib25 article-title: Identifying a clinically applicable mutational burden threshold as a potential biomarker of response to immune checkpoint therapy in solid tumors publication-title: JCO Precis Oncol – volume: 37 start-page: 537 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib35 article-title: Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater publication-title: J Clin Oncol doi: 10.1200/JCO.18.00149 – volume: 58 start-page: 578 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib6 article-title: Tumor mutational burden standardization initiatives: recommendations for consistent tumor mutational burden assessment in clinical samples to guide immunotherapy treatment decisions publication-title: Genes Chromosomes Cancer doi: 10.1002/gcc.22733 – volume: 378 start-page: 2093 year: 2018 ident: 10.1016/j.jtocrr.2022.100431_bib11 article-title: Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden publication-title: N Engl J Med doi: 10.1056/NEJMoa1801946 – volume: 393 start-page: 1819 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib36 article-title: Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial publication-title: Lancet doi: 10.1016/S0140-6736(18)32409-7 – volume: 8 year: 2020 ident: 10.1016/j.jtocrr.2022.100431_bib23 article-title: Establishing guidelines to harmonize tumor mutational burden (TMB): in silico assessment of variation in TMB quantification across diagnostic platforms: phase I of the Friends of Cancer Research TMB Harmonization Project publication-title: J Immunother Cancer – volume: 30 start-page: 863 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib2 article-title: Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up publication-title: Ann Oncol doi: 10.1093/annonc/mdy474 – volume: 362 start-page: eaar3593 year: 2018 ident: 10.1016/j.jtocrr.2022.100431_bib22 article-title: Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy publication-title: Science doi: 10.1126/science.aar3593 – volume: 379 start-page: 2040 year: 2018 ident: 10.1016/j.jtocrr.2022.100431_bib4 article-title: Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer publication-title: N Engl J Med doi: 10.1056/NEJMoa1810865 – volume: 5 year: 2020 ident: 10.1016/j.jtocrr.2022.100431_bib29 article-title: STK11 and KEAP1 mutations as prognostic biomarkers in an observational real-world lung adenocarcinoma cohort publication-title: ESMO Open doi: 10.1136/esmoopen-2020-000706 – volume: 21 start-page: 1353 year: 2020 ident: 10.1016/j.jtocrr.2022.100431_bib26 article-title: Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study publication-title: Lancet Oncol doi: 10.1016/S1470-2045(20)30445-9 – volume: 51 start-page: 202 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib42 article-title: Tumor mutational load predicts survival after immunotherapy across multiple cancer types publication-title: Nat Genet doi: 10.1038/s41588-018-0312-8 – volume: 6 start-page: 661 year: 2020 ident: 10.1016/j.jtocrr.2022.100431_bib32 article-title: Durvalumab with or without tremelimumab vs standard chemotherapy in first-line treatment of metastatic non-small cell lung cancer: the MYSTIC Phase 3 randomized clinical trial publication-title: JAMA Oncol doi: 10.1001/jamaoncol.2020.0237 – ident: 10.1016/j.jtocrr.2022.100431_bib27 – volume: 348 start-page: 124 year: 2015 ident: 10.1016/j.jtocrr.2022.100431_bib9 article-title: Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer publication-title: Science doi: 10.1126/science.aaa1348 – volume: 30 start-page: v916 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib30 article-title: Association between tissue TMB (tTMB) and clinical outcomes with pembrolizumab monotherapy (pembro) in PD-L1-positive advanced NSCLC in the KEYNOTE-010 and −042 trials publication-title: Ann Oncol doi: 10.1093/annonc/mdz394.077 – volume: 80 start-page: CT084 year: 2020 ident: 10.1016/j.jtocrr.2022.100431_bib41 article-title: Relationship between STK11 and KEAP1 mutational status and efficacy in KEYNOTE-042: pembrolizumab monotherapy versus platinum-based chemotherapy as first-line therapy for PD-L1-positive advanced NSCLC publication-title: Cancer Res doi: 10.1158/1538-7445.AM2020-CT084 – volume: 133 start-page: 144 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib19 article-title: Impact of KRAS mutation subtype and concurrent pathogenic mutations on non-small cell lung cancer outcomes publication-title: Lung Cancer doi: 10.1016/j.lungcan.2019.05.015 – volume: 19 start-page: 495 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib17 article-title: Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy publication-title: Nat Rev Cancer doi: 10.1038/s41568-019-0179-8 – volume: 11 start-page: S71 issue: suppl 1 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib10 article-title: Current views on tumor mutational burden in patients with non-small cell lung cancer treated by immune checkpoint inhibitors publication-title: J Thorac Dis doi: 10.21037/jtd.2018.11.102 – volume: 33 start-page: 843 year: 2018 ident: 10.1016/j.jtocrr.2022.100431_bib31 article-title: Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer publication-title: Cancer Cell doi: 10.1016/j.ccell.2018.03.018 – volume: 28 start-page: 75 year: 2017 ident: 10.1016/j.jtocrr.2022.100431_bib21 article-title: Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up publication-title: Ann Oncol doi: 10.1093/annonc/mdw436 – volume: 127 start-page: 2930 year: 2017 ident: 10.1016/j.jtocrr.2022.100431_bib24 article-title: IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade publication-title: J Clin Invest doi: 10.1172/JCI91190 – volume: 10 year: 2022 ident: 10.1016/j.jtocrr.2022.100431_bib28 article-title: Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors publication-title: J Immunother Cancer – volume: 375 start-page: 1823 year: 2016 ident: 10.1016/j.jtocrr.2022.100431_bib34 article-title: Pembrolizumab versus chemotherapy for PD-L1-positive non–small-cell lung cancer publication-title: N Engl J Med doi: 10.1056/NEJMoa1606774 – volume: 79 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib38 article-title: Inactivating STK11/LKB1 genomic alterations are a major driver of primary resistance to PD-1 axis blockade in non-squamous non-small cell lung cancer publication-title: Cancer Res doi: 10.1158/1538-7445.AM2019-SY42-02 – volume: 376 start-page: 2415 year: 2017 ident: 10.1016/j.jtocrr.2022.100431_bib14 article-title: First-line nivolumab in stage IV or recurrent non-small-cell lung cancer publication-title: N Engl J Med doi: 10.1056/NEJMoa1613493 – volume: 27 start-page: 935 year: 2018 ident: 10.1016/j.jtocrr.2022.100431_bib20 article-title: Synergy between the KEAP1/NRF2 and PI3K pathways drives non-small-cell lung cancer with an altered immune microenvironment publication-title: Cell Metab doi: 10.1016/j.cmet.2018.02.006 – volume: 26 start-page: 2354 year: 2020 ident: 10.1016/j.jtocrr.2022.100431_bib37 article-title: Baseline plasma tumor mutation burden predicts response to pembrolizumab-based therapy in patients with metastatic non-small cell lung cancer publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-19-3663 – volume: 36 start-page: 633 year: 2018 ident: 10.1016/j.jtocrr.2022.100431_bib39 article-title: Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing publication-title: J Clin Oncol doi: 10.1200/JCO.2017.75.3384 – volume: 378 start-page: 2078 year: 2018 ident: 10.1016/j.jtocrr.2022.100431_bib3 article-title: Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer publication-title: N Engl J Med doi: 10.1056/NEJMoa1801005 – volume: 7 start-page: 183 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib5 article-title: Tumor mutational burden quantification from targeted gene panels: major advancements and challenges publication-title: J Immunother Cancer doi: 10.1186/s40425-019-0647-4 – volume: 511 start-page: 543 year: 2014 ident: 10.1016/j.jtocrr.2022.100431_bib16 article-title: Comprehensive molecular profiling of lung adenocarcinoma publication-title: Nature doi: 10.1038/nature13385 – volume: 50 start-page: 1271 year: 2018 ident: 10.1016/j.jtocrr.2022.100431_bib40 article-title: Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors publication-title: Nat Genet doi: 10.1038/s41588-018-0200-2 – volume: 4 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib7 article-title: PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers publication-title: JCI Insight doi: 10.1172/jci.insight.126908 – volume: 37 start-page: 992 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib13 article-title: First-line nivolumab plus ipilimumab in advanced non-small-cell lung cancer (CheckMate 568): outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers publication-title: J Clin Oncol doi: 10.1200/JCO.18.01042 – volume: 130 start-page: 50 year: 2019 ident: 10.1016/j.jtocrr.2022.100431_bib18 article-title: Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11 publication-title: Lung Cancer doi: 10.1016/j.lungcan.2019.01.003 – reference: 41089738 - JTO Clin Res Rep. 2025 Sep 02;6(10):100892. doi: 10.1016/j.jtocrr.2025.100892. |
| SSID | ssj0002511782 |
| Score | 2.4059885 |
| Snippet | We evaluated tissue tumor mutational burden (tTMB) and mutations in STK11, KEAP1, and KRAS as biomarkers for outcomes with pembrolizumab plus platinum-based... AbstractIntroductionWe evaluated tissue tumor mutational burden (tTMB) and mutations in STK11, KEAP1, and KRAS as biomarkers for outcomes with pembrolizumab... We evaluated tissue tumor mutational burden (tTMB) and mutations in and as biomarkers for outcomes with pembrolizumab plus platinum-based chemotherapy... Introduction: We evaluated tissue tumor mutational burden (tTMB) and mutations in STK11, KEAP1, and KRAS as biomarkers for outcomes with pembrolizumab plus... |
| SourceID | doaj pubmedcentral proquest pubmed crossref elsevier |
| SourceType | Open Website Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 100431 |
| SubjectTerms | Biomarker Hematology, Oncology, and Palliative Medicine Metastatic non‒small-cell lung cancer Original Pembrolizumab Single-gene genetic alterations Tissue tumor mutational burden |
| Title | Associations of Tissue Tumor Mutational Burden and Mutational Status With Clinical Outcomes With Pembrolizumab Plus Chemotherapy Versus Chemotherapy For Metastatic NSCLC |
| URI | https://www.clinicalkey.com/#!/content/1-s2.0-S2666364322001552 https://www.clinicalkey.es/playcontent/1-s2.0-S2666364322001552 https://dx.doi.org/10.1016/j.jtocrr.2022.100431 https://www.ncbi.nlm.nih.gov/pubmed/36793385 https://www.proquest.com/docview/2777405515 https://pubmed.ncbi.nlm.nih.gov/PMC9923193 https://doaj.org/article/5b31e33aa86a4148993ed9fca9e915ac |
| Volume | 4 |
| WOSCitedRecordID | wos001165404600001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVAON databaseName: DOAJ Directory of Open Access Journals customDbUrl: eissn: 2666-3643 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0002511782 issn: 2666-3643 databaseCode: DOA dateStart: 20200101 isFulltext: true titleUrlDefault: https://www.doaj.org/ providerName: Directory of Open Access Journals – providerCode: PRVHPJ databaseName: ROAD: Directory of Open Access Scholarly Resources customDbUrl: eissn: 2666-3643 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0002511782 issn: 2666-3643 databaseCode: M~E dateStart: 20200101 isFulltext: true titleUrlDefault: https://road.issn.org providerName: ISSN International Centre |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Nj9MwELVghRAXxPd2gZWRuEYkdhI7R6i24kBLpS2iN8uxHW1XbYKaBIk98H_4l4xjp0oWpHLgkoNjx8rMZObZ8bxB6G1hotAQngSFkiyIZR4HuYpUQCE80AScckhcsQm2WPD1OlsOSn3ZM2GOHtgJ7l2S08hQKiVPZQzYHeKp0Rk8OTNZlEhlvW_IssFiyvpgC5xZVykKAlAaUIi7fd5cd7jruqnU3tKBEmLPCcQ0GsWljr5_FJ7-hJ-3T1EOwtLsEXro8SR-797jMbpjyifo_tz_MX-Kfg3kX-OqwKtO0njV7qo9nreN3wzELp8By1IPWy0WbWv8ddNcYU8husWf2wbs1PjmpdnltvTPTbuTOV5uobtlIfCZXT-w3ZG73Tazc5tG2nSmjcKLy-mn6TP0ZXaxmn4MfHmGQKWUNQHXUieRBoRjIl7AIltHWkahpNImhmidqyLVrAAMEicFVzxWYBYs5kUIAzno9Dk6KavSnCKsCSmIiY3KQclGUp5rGRcm1jlLM5KnE0R75QjlucttCY2t6A-pXQunUmFVKpxKJyg4jPrmuDuO9P9g9X7oa5m3uwawR-HtURyzxwlKeqsRfXIruGN40ObI5Oxv40ztfUotIlETEYpLa9HWoAlxBHrDkR42OTj0D3O-6c1agFexv4pkaaq2FoTBsiAENJ1M0Atn5gex0BR8OuVwh40-gJHcxnfKzVXHXJ7Z5URGz_6HoF-iB_Aq1G2HvUInzb41r9E99b3Z1PtzdJet-XnnFOA6_3nxG9Fha2o |
| linkProvider | Directory of Open Access Journals |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Associations+of+Tissue+Tumor+Mutational+Burden+and+Mutational+Status+With+Clinical+Outcomes+With+Pembrolizumab+Plus+Chemotherapy+Versus+Chemotherapy+For+Metastatic+NSCLC&rft.jtitle=JTO+clinical+and+research+reports&rft.au=Marina+C.+Garassino%2C+MD&rft.au=Shirish+Gadgeel%2C+MD&rft.au=Silvia+Novello%2C+MD%2C+PhD&rft.au=Balazs+Halmos%2C+MD&rft.date=2023-01-01&rft.pub=Elsevier&rft.issn=2666-3643&rft.eissn=2666-3643&rft.volume=4&rft.issue=1&rft.spage=100431&rft_id=info:doi/10.1016%2Fj.jtocrr.2022.100431&rft.externalDBID=DOA&rft.externalDocID=oai_doaj_org_article_5b31e33aa86a4148993ed9fca9e915ac |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2666-3643&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2666-3643&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2666-3643&client=summon |