The role of CEA, CYFRA21-1 and NSE in monitoring tumor response to Nivolumab in advanced non-small cell lung cancer (NSCLC) patients.
Adult
Aged
Aged, 80 and over
Antigens, Neoplasm
/ blood
Biomarkers, Tumor
/ blood
Carcinoembryonic Antigen
/ blood
Carcinoma, Non-Small-Cell Lung
/ blood
Disease-Free Survival
Female
Humans
Keratin-19
/ blood
Lung Neoplasms
/ blood
Male
Middle Aged
Neoplasm Staging
Nivolumab
/ therapeutic use
Phosphopyruvate Hydratase
/ blood
CEA
CYFRA21-1
Immunotherapy
NSCLC
Survival
Tumor response
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
08 03 2019
08 03 2019
Historique:
received:
28
09
2018
accepted:
01
03
2019
entrez:
10
3
2019
pubmed:
10
3
2019
medline:
24
4
2020
Statut:
epublish
Résumé
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. 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 Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient's withdrawn from the study.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). 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 30849967
doi: 10.1186/s12967-019-1828-0
pii: 10.1186/s12967-019-1828-0
pmc: PMC6408784
doi:
Substances chimiques
Antigens, Neoplasm
0
Biomarkers, Tumor
0
Carcinoembryonic Antigen
0
Keratin-19
0
antigen CYFRA21.1
0
Nivolumab
31YO63LBSN
Phosphopyruvate Hydratase
EC 4.2.1.11
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
74Références
Anticancer Res. 2014 Sep;34(9):5193-8
pubmed: 25202114
Tumour Biol. 1994;15(6):318-25
pubmed: 7997803
Cancer. 2006 Dec 15;107(12):2842-9
pubmed: 17103443
Cancer Immunol Immunother. 2014 Jul;63(7):675-83
pubmed: 24695951
Onco Targets Ther. 2016 Jun 27;9:3873-8
pubmed: 27390527
Thorax. 1986 Jan;41(1):17-24
pubmed: 3704962
Tumour Biol. 2018 Feb;40(2):1010428318760420
pubmed: 29463190
Semin Respir Crit Care Med. 2016 Oct;37(5):760-770
pubmed: 27732997
Am J Respir Crit Care Med. 2016 Feb 15;193(4):427-37
pubmed: 26465739
Anticancer Res. 2008 Jan-Feb;28(1B):507-13
pubmed: 18383893
Ann Oncol. 2018 Feb 1;29(2):524
pubmed: 28379318
Scand J Clin Lab Invest Suppl. 2016;245:S40-5
pubmed: 27542002
Gut. 1973 Oct;14(10):794-9
pubmed: 4758660
J Crit Care. 2016 Dec;36:18-23
pubmed: 27546742
J Thorac Oncol. 2018 Jan;13(1):97-105
pubmed: 29170120
Br J Cancer. 2017 Apr 11;116(8):1037-1045
pubmed: 28278517
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
Wien Klin Wochenschr. 2015 Jun;127(11-12):465-71
pubmed: 25917364
Anticancer Res. 2018 Jan;38(1):559-563
pubmed: 29277824
Tumour Biol. 2003 Aug-Sep;24(4):209-18
pubmed: 14654716
Cancer Med. 2015 Nov;4(11):1633-8
pubmed: 26333429
Lung Cancer. 2017 Sep;111:176-181
pubmed: 28838390
Tumour Biol. 2011 Aug;32(4):689-95
pubmed: 21409421
Cancer Biomark. 2010;6(3-4):179-90
pubmed: 20660963
Zhongguo Fei Ai Za Zhi. 2016 Aug 20;19(8):550-8
pubmed: 27561807
Cancer Immunol Immunother. 2014 May;63(5):449-58
pubmed: 24609989
Cancer. 2010 Apr 1;116(7):1767-75
pubmed: 20143434
J Cancer. 2014 Sep 05;5(8):663-9
pubmed: 25258647
Pol J Pathol. 2007;58(1):23-33
pubmed: 17585539
Future Oncol. 2014 Jan;10(1):79-90
pubmed: 24328411
N Engl J Med. 2015 Oct 22;373(17):1627-39
pubmed: 26412456
J BUON. 2014 Jan-Mar;19(1):153-6
pubmed: 24659657
Ann Pharmacother. 2015 Aug;49(8):907-37
pubmed: 25991832
Oncotarget. 2016 Nov 22;7(47):77404-77415
pubmed: 27764805
Clin Lab. 2011;57(11-12):1011-4
pubmed: 22239035
Cancer Biomark. 2010;6(3-4):191-6
pubmed: 20660964
N Engl J Med. 2015 Jul 9;373(2):123-35
pubmed: 26028407
Br J Cancer. 2016 Feb 2;114(3):256-61
pubmed: 26794281
Br J Cancer. 2017 Sep 26;117(7):913-920
pubmed: 28950287
Drug Discov Today. 2017 Aug;22(8):1266-1273
pubmed: 28600190
Korean J Thorac Cardiovasc Surg. 2013 Jun;46(3):192-6
pubmed: 23772406