A Molecular Epidemiological Analysis Of Programmed Cell Death Ligand-1 (PD-L1) Protein Expression, Mutations And Survival In Non-Small Cell Lung Cancer
Matthew B Schabath,1,2 Tapashi B Dalvi,3 Hongyue A Dai,4 Alan L Crim,4 Anita Midha,5 Norah Shire,3 Nicholas T Gimbrone,1 Jill Walker,6 Danielle M Greenawalt,7 David Lawrence,8 James R Rigas,9 Robert Brody,9 Danielle Potter,9 Naveen S Kumar,4 Shane A Huntsman,4 Jhanelle E Gray2 1Department of Cancer...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-11-01
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| Series: | Cancer Management and Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/a-molecular-epidemiological-analysis-of-programmed-cell-death-ligand-1-peer-reviewed-article-CMAR |
| _version_ | 1828772481774649344 |
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| author | Schabath MB Dalvi TB Dai HA Crim AL Midha A Shire N Gimbrone NT Walker J Greenawalt DM Lawrence D Rigas JR Brody R Potter D Kumar NS Huntsman SA Gray JE |
| author_facet | Schabath MB Dalvi TB Dai HA Crim AL Midha A Shire N Gimbrone NT Walker J Greenawalt DM Lawrence D Rigas JR Brody R Potter D Kumar NS Huntsman SA Gray JE |
| author_sort | Schabath MB |
| collection | DOAJ |
| description | Matthew B Schabath,1,2 Tapashi B Dalvi,3 Hongyue A Dai,4 Alan L Crim,4 Anita Midha,5 Norah Shire,3 Nicholas T Gimbrone,1 Jill Walker,6 Danielle M Greenawalt,7 David Lawrence,8 James R Rigas,9 Robert Brody,9 Danielle Potter,9 Naveen S Kumar,4 Shane A Huntsman,4 Jhanelle E Gray2 1Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 2Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 3Oncology R&D, AstraZeneca, Gaithersburg, MD, USA; 4M2Gen, Tampa, FL, USA; 5Department of Personalised Healthcare and Biomarkers, AstraZeneca, Cambridge, UK; 6Department of Precision Medicine Oncology, AstraZeneca, Cambridge, UK; 7Department of iMED Oncology Informatics, AstraZeneca, Waltham, MA, USA; 8Department of Global Medicines Development, AstraZeneca, Cambridge, UK; 9Department of Global Medical Affairs Oncology, AstraZeneca, Gaithersburg, MD, USACorrespondence: Matthew B SchabathH. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USATel +1 813 745 4150Fax +1 813 745 6525Email matthew.schabath@moffitt.orgPurpose: To characterize programmed cell death ligand-1 (PD-L1) expression in relation to survival and gene mutation status in patients with advanced NSCLC. The study also explored the influence of tumor mutational burden (TMB) on PD-L1 expression and patient characteristics.Patients and methods: Adult patients with histologically or cytologically documented Stage IIIB/Stage IV/recurrent/progressive NSCLC, Eastern Cooperative Oncology Group performance status 0 to 3, and >2 lines of prior systemic treatment regimens were included in this retrospective analysis. Patients were treated from 1997 to 2015 at H. Lee Moffitt Cancer Center and Research Institute, Tampa, or at 7 community centers across the United States. PD-L1 expression level was determined using the VENTANA PD-L1 (SP263) Assay. EGFR and KRAS mutation status and ALK rearrangements were determined by targeted DNA sequencing; these were obtained from clinical records where targeted DNA sequencing was not performed. TMB was calculated as the total number of somatic mutations per sample.Results: From a total of 136 patients included in the study, 23.5% had tumors with high PD-L1 expression (≥25%). There were no significant differences in patient characteristics, overall survival (OS), and progression-free survival (PFS) between patients with high PD-L1 expression (median OS: 39.5 months; median PFS: 15.8 months) vs low PD-L1 expression (<25%; median OS: 38.1 months; median PFS: 18.6 months). PD-L1 expression level correlated (P=0.05) with TMB and was consistent with The Cancer Genome Atlas data.Conclusion: In this retrospective analysis, survival outcomes of patients with advanced NSCLC were comparable by PD-L1 expression level. EGFR and KRAS mutation status were not found to be significantly associated with PD-L1 expression level, while TMB was weakly associated with PD-L1 expression level. Overall, PD-L1 expression level was not observed to be an independent prognostic biomarker in this cohort of patients with advanced NSCLC treated with chemotherapy.Keywords: non-small cell lung cancer, patient outcomes, tumor mutational burden, prognostic biomarker |
| first_indexed | 2024-12-11T14:44:45Z |
| format | Article |
| id | doaj.art-9fa4072c11ab49a1b2f66db914195bae |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-11T14:44:45Z |
| publishDate | 2019-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-9fa4072c11ab49a1b2f66db914195bae2022-12-22T01:01:44ZengDove Medical PressCancer Management and Research1179-13222019-11-01Volume 119469948149604A Molecular Epidemiological Analysis Of Programmed Cell Death Ligand-1 (PD-L1) Protein Expression, Mutations And Survival In Non-Small Cell Lung CancerSchabath MBDalvi TBDai HACrim ALMidha AShire NGimbrone NTWalker JGreenawalt DMLawrence DRigas JRBrody RPotter DKumar NSHuntsman SAGray JEMatthew B Schabath,1,2 Tapashi B Dalvi,3 Hongyue A Dai,4 Alan L Crim,4 Anita Midha,5 Norah Shire,3 Nicholas T Gimbrone,1 Jill Walker,6 Danielle M Greenawalt,7 David Lawrence,8 James R Rigas,9 Robert Brody,9 Danielle Potter,9 Naveen S Kumar,4 Shane A Huntsman,4 Jhanelle E Gray2 1Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 2Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 3Oncology R&D, AstraZeneca, Gaithersburg, MD, USA; 4M2Gen, Tampa, FL, USA; 5Department of Personalised Healthcare and Biomarkers, AstraZeneca, Cambridge, UK; 6Department of Precision Medicine Oncology, AstraZeneca, Cambridge, UK; 7Department of iMED Oncology Informatics, AstraZeneca, Waltham, MA, USA; 8Department of Global Medicines Development, AstraZeneca, Cambridge, UK; 9Department of Global Medical Affairs Oncology, AstraZeneca, Gaithersburg, MD, USACorrespondence: Matthew B SchabathH. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USATel +1 813 745 4150Fax +1 813 745 6525Email matthew.schabath@moffitt.orgPurpose: To characterize programmed cell death ligand-1 (PD-L1) expression in relation to survival and gene mutation status in patients with advanced NSCLC. The study also explored the influence of tumor mutational burden (TMB) on PD-L1 expression and patient characteristics.Patients and methods: Adult patients with histologically or cytologically documented Stage IIIB/Stage IV/recurrent/progressive NSCLC, Eastern Cooperative Oncology Group performance status 0 to 3, and >2 lines of prior systemic treatment regimens were included in this retrospective analysis. Patients were treated from 1997 to 2015 at H. Lee Moffitt Cancer Center and Research Institute, Tampa, or at 7 community centers across the United States. PD-L1 expression level was determined using the VENTANA PD-L1 (SP263) Assay. EGFR and KRAS mutation status and ALK rearrangements were determined by targeted DNA sequencing; these were obtained from clinical records where targeted DNA sequencing was not performed. TMB was calculated as the total number of somatic mutations per sample.Results: From a total of 136 patients included in the study, 23.5% had tumors with high PD-L1 expression (≥25%). There were no significant differences in patient characteristics, overall survival (OS), and progression-free survival (PFS) between patients with high PD-L1 expression (median OS: 39.5 months; median PFS: 15.8 months) vs low PD-L1 expression (<25%; median OS: 38.1 months; median PFS: 18.6 months). PD-L1 expression level correlated (P=0.05) with TMB and was consistent with The Cancer Genome Atlas data.Conclusion: In this retrospective analysis, survival outcomes of patients with advanced NSCLC were comparable by PD-L1 expression level. EGFR and KRAS mutation status were not found to be significantly associated with PD-L1 expression level, while TMB was weakly associated with PD-L1 expression level. Overall, PD-L1 expression level was not observed to be an independent prognostic biomarker in this cohort of patients with advanced NSCLC treated with chemotherapy.Keywords: non-small cell lung cancer, patient outcomes, tumor mutational burden, prognostic biomarkerhttps://www.dovepress.com/a-molecular-epidemiological-analysis-of-programmed-cell-death-ligand-1-peer-reviewed-article-CMARnon-small cell lung cancerpatient outcomestumor mutational burdenprognostic biomarker |
| spellingShingle | Schabath MB Dalvi TB Dai HA Crim AL Midha A Shire N Gimbrone NT Walker J Greenawalt DM Lawrence D Rigas JR Brody R Potter D Kumar NS Huntsman SA Gray JE A Molecular Epidemiological Analysis Of Programmed Cell Death Ligand-1 (PD-L1) Protein Expression, Mutations And Survival In Non-Small Cell Lung Cancer Cancer Management and Research non-small cell lung cancer patient outcomes tumor mutational burden prognostic biomarker |
| title | A Molecular Epidemiological Analysis Of Programmed Cell Death Ligand-1 (PD-L1) Protein Expression, Mutations And Survival In Non-Small Cell Lung Cancer |
| title_full | A Molecular Epidemiological Analysis Of Programmed Cell Death Ligand-1 (PD-L1) Protein Expression, Mutations And Survival In Non-Small Cell Lung Cancer |
| title_fullStr | A Molecular Epidemiological Analysis Of Programmed Cell Death Ligand-1 (PD-L1) Protein Expression, Mutations And Survival In Non-Small Cell Lung Cancer |
| title_full_unstemmed | A Molecular Epidemiological Analysis Of Programmed Cell Death Ligand-1 (PD-L1) Protein Expression, Mutations And Survival In Non-Small Cell Lung Cancer |
| title_short | A Molecular Epidemiological Analysis Of Programmed Cell Death Ligand-1 (PD-L1) Protein Expression, Mutations And Survival In Non-Small Cell Lung Cancer |
| title_sort | molecular epidemiological analysis of programmed cell death ligand 1 pd l1 protein expression mutations and survival in non small cell lung cancer |
| topic | non-small cell lung cancer patient outcomes tumor mutational burden prognostic biomarker |
| url | https://www.dovepress.com/a-molecular-epidemiological-analysis-of-programmed-cell-death-ligand-1-peer-reviewed-article-CMAR |
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