Soluble Epidermal Growth Factor Receptor (sEGFR) and Carcinoembryonic Antigen (CEA) Concentration in Patients with Non-small Cell Lung Cancer: Correlation with Survival After Erlotinib and Gefitinib Treatment

Overview

Journal Ecancermedicalscience

Specialty Oncology

Date 2012 Jan 26

PMID 22276032

Citations 7

Authors

I Kappers

M A Vollebergh

H van Tinteren

C M Korse

L L Nieuwenhuis

J M G Bonfrer

H M Klomp

N van Zandwijk

M M van den Heuvel

Affiliations

Soon will be listed here.

Abstract

Background: In patients with non-small cell lung cancer (NSCLC), a higher response rate can be achieved with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) when selection for therapy is guided by mutation analysis or gene amplification. However, both tests are complex and require tumour tissue. Simple methods to identify responders prior to EGFR-TKI treatment are urgently needed. This study aimed to define the relation between serum sEGFR levels, carcinoembryonic antigen (CEA) and survival in NSCLC patients treated with EGFR-TKIs.

Methods: Patients with stage III/IV NSCLC treated with gefitinib or erlotinib between July 2002 and December 2005 were reviewed. Levels of serum soluble EGFR (sEGFR) were determined by a sandwich quantitative enzyme-linked immunosorbent assay. A chemiluminescence immunoassay was used for CEA. The relation between sEGFR and survival was investigated.

Results: One hundred and two NSCLC patients, mainly stage IV (80%), were identified. Mean sEGFR at baseline was 55.9 μg/l (range 35.3-74.5 μg/l). The median CEA level was 11.1 μg/l (range <1.0-2938.0 μg/l). Median overall survival was 5.2 months (range 1-52 months). Decreasing log CEA values (HR 1.51, 95% CI 1.11-2.04, multivariate analysis) and increasing sEGFR values (HR 0.96, 95% CI 0.93-0.99, multivariate analysis) were both independently associated with prolonged survival. Higher levels of pre-treatment sEGFR were associated with lower risk of progressive disease within three months (p=0.04).

Conclusions: Both baseline sEGFR and CEA levels in NSCLC patients receiving EGFR-TKIs showed a significant correlation with survival. To distinguish whether these factors have a predictive or a prognostic value, validation is warranted in an independent patient series containing a control arm without EGFR-TKI treatment.

Citing Articles

The Prediction Of Epidermal Growth Factor Receptor Mutation And Prognosis Of EGFR Tyrosine Kinase Inhibitor By Serum Ferritin In Advanced NSCLC.

Wu Z, Dai Y, Chen L Cancer Manag Res. 2019; 11:8835-8843.

PMID: 31632143 PMC: 6789963. DOI: 10.2147/CMAR.S216037.

Safety and efficacy of afatinib as add-on to standard therapy of gemcitabine/cisplatin in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, phase I trial with an extensive biomarker program.

Moehler M, Maderer A, Ehrlich A, Foerster F, Schad A, Nickolay T BMC Cancer. 2019; 19(1):55.

PMID: 30634942 PMC: 6330479. DOI: 10.1186/s12885-018-5223-7.

Gefitinib provides similar effectiveness and improved safety than erlotinib for advanced non-small cell lung cancer: A meta-analysis.

Zhang W, Wei Y, Yu D, Xu J, Peng J Medicine (Baltimore). 2018; 97(16):e0460.

PMID: 29668619 PMC: 5916648. DOI: 10.1097/MD.0000000000010460.

Pretreatment levels of the serum biomarkers CEA, CYFRA 21-1, SCC and the soluble EGFR and its ligands EGF, TGF-alpha, HB-EGF in the prediction of outcome in erlotinib treated non-small-cell lung cancer patients.

Romero-Ventosa E, Blanco-Prieto S, Gonzalez-Pineiro A, Rodriguez-Berrocal F, Pineiro-Corrales G, Paez de la Cadena M Springerplus. 2015; 4:171.

PMID: 25918681 PMC: 4402684. DOI: 10.1186/s40064-015-0891-0.

CEA serum level as early predictive marker of outcome during EGFR-TKI therapy in advanced NSCLC patients.

Facchinetti F, Aldigeri R, Aloe R, Bortesi B, Ardizzoni A, Tiseo M Tumour Biol. 2015; 36(8):5943-51.

PMID: 25731731 DOI: 10.1007/s13277-015-3269-6.

References

Shepherd F, Pereira J, Ciuleanu T, Tan E, Hirsh V, Thongprasert S . Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005; 353(2):123-32. DOI: 10.1056/NEJMoa050753. View

Gregorc V, Ceresoli G, Floriani I, Spreafico A, Bencardino K, Ludovini V . Effects of gefitinib on serum epidermal growth factor receptor and HER2 in patients with advanced non-small cell lung cancer. Clin Cancer Res. 2004; 10(18 Pt 1):6006-12. DOI: 10.1158/1078-0432.CCR-03-0770. View

Schneider J, Presek P, Braun A, Bauer P, Konietzko N, Wiesner B . p53 protein, EGF receptor, and anti-p53 antibodies in serum from patients with occupationally derived lung cancer. Br J Cancer. 1999; 80(12):1987-94. PMC: 2363153. DOI: 10.1038/sj.bjc.6690632. View

Kris M, Natale R, Herbst R, Lynch Jr T, Prager D, Belani C . Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003; 290(16):2149-58. DOI: 10.1001/jama.290.16.2149. View

CONCANNON J, Dalbow M, Hodgson S, Headings J, Markopoulos E, Mitchell J . Prognostic value of preoperative carcinoembryonic antigen (CEA) plasma levels in patients with bronchogenic carcinoma. Cancer. 1978; 42(3 Suppl):1477-83. DOI: 10.1002/1097-0142(197809)42:3+<1477::aid-cncr2820420818>3.0.co;2-e. View

Screaton R, Penn L, Stanners C . Carcinoembryonic antigen, a human tumor marker, cooperates with Myc and Bcl-2 in cellular transformation. J Cell Biol. 1997; 137(4):939-52. PMC: 2139844. DOI: 10.1083/jcb.137.4.939. View

Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard J . Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol. 2003; 21(12):2237-46. DOI: 10.1200/JCO.2003.10.038. View

Molina R, Bonfrer J, Banfi G, Bugugnani M, Cornu F, Hannemann-Pohl K . External evaluation of LIAISON tumour marker assays on the fully automated chemiluminescent LIAISON immunoassay analyser. Clin Lab. 2000; 46(3-4):169-79. View

Thatcher N, Chang A, Parikh P, Pereira J, Ciuleanu T, von Pawel J . Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005; 366(9496):1527-37. DOI: 10.1016/S0140-6736(05)67625-8. View

10.

Lynch T, Bell D, Sordella R, Gurubhagavatula S, Okimoto R, Brannigan B . Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004; 350(21):2129-39. DOI: 10.1056/NEJMoa040938. View

11.

Cappuzzo F, Hirsch F, Rossi E, Bartolini S, Ceresoli G, Bemis L . Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst. 2005; 97(9):643-55. DOI: 10.1093/jnci/dji112. View

12.

Okamoto T, Nakamura T, Ikeda J, Maruyama R, Shoji F, Miyake T . Serum carcinoembryonic antigen as a predictive marker for sensitivity to gefitinib in advanced non-small cell lung cancer. Eur J Cancer. 2005; 41(9):1286-90. DOI: 10.1016/j.ejca.2005.03.011. View

13.

Partanen R, Hemminki K, Koskinen H, Luo J, Carney W, Brandt-Rauf P . The detection of increased amounts of the extracellular domain of the epidermal growth factor receptor in serum during carcinogenesis in asbestosis patients. J Occup Med. 1994; 36(12):1324-8. DOI: 10.1097/00043764-199412000-00013. View

14.

Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I . EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A. 2004; 101(36):13306-11. PMC: 516528. DOI: 10.1073/pnas.0405220101. View

15.

Hirsch F, Varella-Garcia M, Bunn Jr P, Franklin W, Dziadziuszko R, Thatcher N . Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J Clin Oncol. 2006; 24(31):5034-42. DOI: 10.1200/JCO.2006.06.3958. View

16.

Ordonez C, Screaton R, Ilantzis C, Stanners C . Human carcinoembryonic antigen functions as a general inhibitor of anoikis. Cancer Res. 2000; 60(13):3419-24. View

17.

Lemos-Gonzalez Y, Rodriguez-Berrocal F, Cordero O, Gomez C, Paez de la Cadena M . Alteration of the serum levels of the epidermal growth factor receptor and its ligands in patients with non-small cell lung cancer and head and neck carcinoma. Br J Cancer. 2007; 96(10):1569-78. PMC: 2359945. DOI: 10.1038/sj.bjc.6603770. View

18.

Miller V, Kris M, Shah N, Patel J, Azzoli C, Gomez J . Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol. 2004; 22(6):1103-9. DOI: 10.1200/JCO.2004.08.158. View

19.

McShane L, Altman D, Sauerbrei W, Taube S, Gion M, Clark G . REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer. 2005; 93(4):387-91. PMC: 2361579. DOI: 10.1038/sj.bjc.6602678. View

20.

Baron A, Lafky J, Boardman C, Balasubramaniam S, Suman V, Podratz K . Serum sErbB1 and epidermal growth factor levels as tumor biomarkers in women with stage III or IV epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev. 1999; 8(2):129-37. View