The role of CEA, CYFRA21-1 and NSE in monitoring tumor response to Nivolumab in advanced non-small cell lung cancer (NSCLC) patients

M. G. Dal Bello, R. A. Filiberti, A. Alama, A. M. Orengo, M. Mussap, S. Coco, I. Vanni, S. Boccardo, E. Rijavec, C. Genova, F. Biello, G. Barletta, G. Rossi, M. Tagliamento, C. Maggioni, F. Grossi

Research output: Contribution to journalArticle

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Abstract

Background: CEA, CYFRA21-1 and NSE are tumor markers used for monitoring the response to chemotherapy in advanced adenocarcinoma, squamous cell carcinoma and small-cell lung cancer, respectively. Their role in cancer immunotherapy needs to be elucidated. Methods: Patients with advanced non-small cell lung cancer (NSCLC) were treated with nivolumab 3 mg/kg every 2 weeks within the Italian Nivolumab Expanded Access Program. Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient's withdrawn from the study. All patients underwent a CT-scan after every 4 cycles of treatment and responses were classified according to RECIST 1.1. The biomarkers serum levels were measured with a chemiluminescent microparticle immunoassay for CEA and with an immuno radiometric assay for CYFRA21-1 and NSE. The markers values at baseline and after 4 cycles were used to analyze the relationship between their variation over baseline and the tumor response, evaluated as disease control rate (DCR: CR + PR + SD), and survival (PFS and OS). Results: A total of 70 patients were evaluable for the analysis. Overall, a disease control was obtained in 24 patients (35.8%, 4 PR + 20 SD). After 4 cycles of nivolumab a CEA or CYFRA21-1 reduction ≥ 20% over the baseline was significantly associated with DCR (CEA, p = 0.021; CYFRA21-1, p < 0.001), PFS (CEA, p = 0.028; CYFRA21-1, p < 0.001) and OS (CEA, p = 0.026; CYFRA21-1, p = 0.019). Multivariate analysis confirmed the ability of CYFRA21-1 reduction ≥ 20% to predict DCR (p = 0.002) and PFS (p < 0.001). Conclusion: The reduction in serum level of CYFRA21-1 or CEA might be a reliable biomarker to predict immunotherapy efficacy in NSCLC patients. NSE was not significant for monitoring the efficacy of nivolumab.

Original languageEnglish
Article number74
JournalJournal of Translational Medicine
Volume17
Issue number1
DOIs
Publication statusPublished - Mar 8 2019

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Non-Small Cell Lung Carcinoma
Tumors
Cells
Disease control
Monitoring
Biomarkers
Neoplasms
Immunotherapy
Chemotherapy
Computerized tomography
Tumor Biomarkers
Assays
Blood
Small Cell Lung Carcinoma
Serum
Immunoassay
nivolumab
Squamous Cell Carcinoma
Adenocarcinoma
Multivariate Analysis

Keywords

  • CEA
  • CYFRA21-1
  • Immunotherapy
  • NSCLC
  • Survival
  • Tumor response

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The role of CEA, CYFRA21-1 and NSE in monitoring tumor response to Nivolumab in advanced non-small cell lung cancer (NSCLC) patients. / Dal Bello, M. G.; Filiberti, R. A.; Alama, A.; Orengo, A. M.; Mussap, M.; Coco, S.; Vanni, I.; Boccardo, S.; Rijavec, E.; Genova, C.; Biello, F.; Barletta, G.; Rossi, G.; Tagliamento, M.; Maggioni, C.; Grossi, F.

In: Journal of Translational Medicine, Vol. 17, No. 1, 74, 08.03.2019.

Research output: Contribution to journalArticle

Dal Bello, MG, Filiberti, RA, Alama, A, Orengo, AM, Mussap, M, Coco, S, Vanni, I, Boccardo, S, Rijavec, E, Genova, C, Biello, F, Barletta, G, Rossi, G, Tagliamento, M, Maggioni, C & Grossi, F 2019, 'The role of CEA, CYFRA21-1 and NSE in monitoring tumor response to Nivolumab in advanced non-small cell lung cancer (NSCLC) patients', Journal of Translational Medicine, vol. 17, no. 1, 74. https://doi.org/10.1186/s12967-019-1828-0
Dal Bello, M. G. ; Filiberti, R. A. ; Alama, A. ; Orengo, A. M. ; Mussap, M. ; Coco, S. ; Vanni, I. ; Boccardo, S. ; Rijavec, E. ; Genova, C. ; Biello, F. ; Barletta, G. ; Rossi, G. ; Tagliamento, M. ; Maggioni, C. ; Grossi, F. / The role of CEA, CYFRA21-1 and NSE in monitoring tumor response to Nivolumab in advanced non-small cell lung cancer (NSCLC) patients. In: Journal of Translational Medicine. 2019 ; Vol. 17, No. 1.
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title = "The role of CEA, CYFRA21-1 and NSE in monitoring tumor response to Nivolumab in advanced non-small cell lung cancer (NSCLC) patients",
abstract = "Background: CEA, CYFRA21-1 and NSE are tumor markers used for monitoring the response to chemotherapy in advanced adenocarcinoma, squamous cell carcinoma and small-cell lung cancer, respectively. Their role in cancer immunotherapy needs to be elucidated. Methods: Patients with advanced non-small cell lung cancer (NSCLC) were treated with nivolumab 3 mg/kg every 2 weeks within the Italian Nivolumab Expanded Access Program. Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient's withdrawn from the study. All patients underwent a CT-scan after every 4 cycles of treatment and responses were classified according to RECIST 1.1. The biomarkers serum levels were measured with a chemiluminescent microparticle immunoassay for CEA and with an immuno radiometric assay for CYFRA21-1 and NSE. The markers values at baseline and after 4 cycles were used to analyze the relationship between their variation over baseline and the tumor response, evaluated as disease control rate (DCR: CR + PR + SD), and survival (PFS and OS). Results: A total of 70 patients were evaluable for the analysis. Overall, a disease control was obtained in 24 patients (35.8{\%}, 4 PR + 20 SD). After 4 cycles of nivolumab a CEA or CYFRA21-1 reduction ≥ 20{\%} over the baseline was significantly associated with DCR (CEA, p = 0.021; CYFRA21-1, p < 0.001), PFS (CEA, p = 0.028; CYFRA21-1, p < 0.001) and OS (CEA, p = 0.026; CYFRA21-1, p = 0.019). Multivariate analysis confirmed the ability of CYFRA21-1 reduction ≥ 20{\%} to predict DCR (p = 0.002) and PFS (p < 0.001). Conclusion: The reduction in serum level of CYFRA21-1 or CEA might be a reliable biomarker to predict immunotherapy efficacy in NSCLC patients. NSE was not significant for monitoring the efficacy of nivolumab.",
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T1 - The role of CEA, CYFRA21-1 and NSE in monitoring tumor response to Nivolumab in advanced non-small cell lung cancer (NSCLC) patients

AU - Dal Bello, M. G.

AU - Filiberti, R. A.

AU - Alama, A.

AU - Orengo, A. M.

AU - Mussap, M.

AU - Coco, S.

AU - Vanni, I.

AU - Boccardo, S.

AU - Rijavec, E.

AU - Genova, C.

AU - Biello, F.

AU - Barletta, G.

AU - Rossi, G.

AU - Tagliamento, M.

AU - Maggioni, C.

AU - Grossi, F.

PY - 2019/3/8

Y1 - 2019/3/8

N2 - Background: CEA, CYFRA21-1 and NSE are tumor markers used for monitoring the response to chemotherapy in advanced adenocarcinoma, squamous cell carcinoma and small-cell lung cancer, respectively. Their role in cancer immunotherapy needs to be elucidated. Methods: Patients with advanced non-small cell lung cancer (NSCLC) were treated with nivolumab 3 mg/kg every 2 weeks within the Italian Nivolumab Expanded Access Program. Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient's withdrawn from the study. All patients underwent a CT-scan after every 4 cycles of treatment and responses were classified according to RECIST 1.1. The biomarkers serum levels were measured with a chemiluminescent microparticle immunoassay for CEA and with an immuno radiometric assay for CYFRA21-1 and NSE. The markers values at baseline and after 4 cycles were used to analyze the relationship between their variation over baseline and the tumor response, evaluated as disease control rate (DCR: CR + PR + SD), and survival (PFS and OS). Results: A total of 70 patients were evaluable for the analysis. Overall, a disease control was obtained in 24 patients (35.8%, 4 PR + 20 SD). After 4 cycles of nivolumab a CEA or CYFRA21-1 reduction ≥ 20% over the baseline was significantly associated with DCR (CEA, p = 0.021; CYFRA21-1, p < 0.001), PFS (CEA, p = 0.028; CYFRA21-1, p < 0.001) and OS (CEA, p = 0.026; CYFRA21-1, p = 0.019). Multivariate analysis confirmed the ability of CYFRA21-1 reduction ≥ 20% to predict DCR (p = 0.002) and PFS (p < 0.001). Conclusion: The reduction in serum level of CYFRA21-1 or CEA might be a reliable biomarker to predict immunotherapy efficacy in NSCLC patients. NSE was not significant for monitoring the efficacy of nivolumab.

AB - Background: CEA, CYFRA21-1 and NSE are tumor markers used for monitoring the response to chemotherapy in advanced adenocarcinoma, squamous cell carcinoma and small-cell lung cancer, respectively. Their role in cancer immunotherapy needs to be elucidated. Methods: Patients with advanced non-small cell lung cancer (NSCLC) were treated with nivolumab 3 mg/kg every 2 weeks within the Italian Nivolumab Expanded Access Program. Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient's withdrawn from the study. All patients underwent a CT-scan after every 4 cycles of treatment and responses were classified according to RECIST 1.1. The biomarkers serum levels were measured with a chemiluminescent microparticle immunoassay for CEA and with an immuno radiometric assay for CYFRA21-1 and NSE. The markers values at baseline and after 4 cycles were used to analyze the relationship between their variation over baseline and the tumor response, evaluated as disease control rate (DCR: CR + PR + SD), and survival (PFS and OS). Results: A total of 70 patients were evaluable for the analysis. Overall, a disease control was obtained in 24 patients (35.8%, 4 PR + 20 SD). After 4 cycles of nivolumab a CEA or CYFRA21-1 reduction ≥ 20% over the baseline was significantly associated with DCR (CEA, p = 0.021; CYFRA21-1, p < 0.001), PFS (CEA, p = 0.028; CYFRA21-1, p < 0.001) and OS (CEA, p = 0.026; CYFRA21-1, p = 0.019). Multivariate analysis confirmed the ability of CYFRA21-1 reduction ≥ 20% to predict DCR (p = 0.002) and PFS (p < 0.001). Conclusion: The reduction in serum level of CYFRA21-1 or CEA might be a reliable biomarker to predict immunotherapy efficacy in NSCLC patients. NSE was not significant for monitoring the efficacy of nivolumab.

KW - CEA

KW - CYFRA21-1

KW - Immunotherapy

KW - NSCLC

KW - Survival

KW - Tumor response

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U2 - 10.1186/s12967-019-1828-0

DO - 10.1186/s12967-019-1828-0

M3 - Article

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JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

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