Epidermal Growth Factor Receptor is Associated with the Onset of Skeletal Related Events in Non-small Cell Lung Cancer

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Nov 9

PMID 29113396

Citations 5

Authors

Shu-Mei Huang

Jin-Ji Yang

Hua-Jun Chen

Si-Pei Wu

Xiao-Yan Bai

Qing Zhou

Hai-Yan Tu

Yi-Long Wu

Affiliations

Soon will be listed here.

Abstract

Background: Bone metastasis and skeletal related events (SREs) are common in non-small cell lung cancer (NSCLC). Patients with mutant epidermal growth factor receptor (EGFR) could benefit from tyrosine kinase inhibitors (TKIs). However, it is unclear whether SRE is influenced by EGFR status. We aimed to evaluate the correlation of EGFR status and TKIs with the incidence of SREs.

Methods: We conducted a retrospective study of stage IV NSCLC patients with bone metastasis. Incidence rate of SREs was collected and was compared using chi-square test. Logistic-regression analysis was used to identify the risk factors predicting the incidence of SREs.

Results: 410 eligible patients were enrolled in the study. 49.0% were detected with EGFR mutation. 49.8% of patients received EGFR-TKIs therapy prior to the onset of SREs. 42.7% experienced at least one SRE. Patients who were treated with TKIs held lower incidence of SREs than patients who were not treated with TKIs (23.5% vs 61.7%, ). Multivariate analysis showed that poor performance status (OR 5.550, 95%CI 2.290-13.450; ) and mutant EGFR (OR 3.050, 95%CI 1.608-5.787, ) were independent risk factors predicting the onset of SREs, while the usage of TKIs (OR 0.102, 95%CI 0.054-0.193, ) was a protective factor of SREs in NSCLC patients with bone metastasis.

Conclusions: This study indicates that the incidence of SREs is common in both patients with and without EGFR mutation. Poor performance ability and mutant EGFR imply higher risks of SREs, while the usage of TKIs may be a protective factor of SREs.

Citing Articles

Femoral bone metastasis is a poor prognostic factor in EGFR-TKIs-treated patients with -mutated non-small-cell lung cancer: a retrospective, multicenter cohort study.

Tanaka I, Hori K, Koyama J, Gen S, Morise M, Kodama Y Ther Adv Med Oncol. 2024; 16:17588359241303090.

PMID: 39712073 PMC: 11662391. DOI: 10.1177/17588359241303090.

Overall Survival Improvement in Patients with Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer and Bone Metastasis Treated with Denosumab.

Ko H, Chiu C, Wang C, Yang T, Liu C, Yu C Cancers (Basel). 2022; 14(14).

PMID: 35884531 PMC: 9316991. DOI: 10.3390/cancers14143470.

Reporting of Incidence and Outcome of Bone Metastases in Clinical Trials Enrolling Patients with Epidermal Growth Factor Receptor Mutated Lung Adenocarcinoma-A Systematic Review.

Brouns A, Dursun S, Bootsma G, Dingemans A, Hendriks L Cancers (Basel). 2021; 13(13).

PMID: 34201833 PMC: 8267949. DOI: 10.3390/cancers13133144.

High Prevalence and Early Occurrence of Skeletal Complications in EGFR Mutated NSCLC Patients With Bone Metastases.

Lagana M, Gurizzan C, Roca E, Cortinovis D, Signorelli D, Pagani F Front Oncol. 2020; 10:588862.

PMID: 33282740 PMC: 7689017. DOI: 10.3389/fonc.2020.588862.

Risk factors for bone metastasis in patients with primary lung cancer: A systematic review.

Niu Y, Lin Y, Pang H, Shen W, Liu L, Zhang H Medicine (Baltimore). 2019; 98(3):e14084.

PMID: 30653124 PMC: 6370015. DOI: 10.1097/MD.0000000000014084.

References

Zhou Q, Zhang X, Chen Z, Yin X, Yang J, Xu C . Relative abundance of EGFR mutations predicts benefit from gefitinib treatment for advanced non-small-cell lung cancer. J Clin Oncol. 2011; 29(24):3316-21. DOI: 10.1200/JCO.2010.33.3757. View

Katakami N, Kunikane H, Takeda K, Takayama K, Sawa T, Saito H . Prospective study on the incidence of bone metastasis (BM) and skeletal-related events (SREs) in patients (pts) with stage IIIB and IV lung cancer-CSP-HOR 13. J Thorac Oncol. 2014; 9(2):231-8. PMC: 4132043. DOI: 10.1097/JTO.0000000000000051. View

Travis W . Pathology of lung cancer. Clin Chest Med. 2011; 32(4):669-92. DOI: 10.1016/j.ccm.2011.08.005. View

Furugaki K, Moriya Y, Iwai T, Yorozu K, Yanagisawa M, Kondoh K . Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292. Clin Exp Metastasis. 2011; 28(7):649-59. PMC: 3198194. DOI: 10.1007/s10585-011-9398-4. View

Aiba H, Kimura T, Yamagami T, Watanabe N, Sakurai H, Kimura H . Prediction of skeletal-related events in patients with non-small cell lung cancer. Support Care Cancer. 2016; 24(8):3361-7. DOI: 10.1007/s00520-016-3167-5. View

Pluquet E, Cadranel J, Legendre A, Faller M, Souquet P, Zalcman G . Osteoblastic reaction in non-small cell lung carcinoma and its association to epidermal growth factor receptor tyrosine kinase inhibitors response and prolonged survival. J Thorac Oncol. 2010; 5(4):491-6. DOI: 10.1097/JTO.0b013e3181cf0440. View

Santini D, Daniele S, Barni S, Sandro B, Intagliata S, Salvatore I . Natural History of Non-Small-Cell Lung Cancer with Bone Metastases. Sci Rep. 2015; 5:18670. PMC: 4687045. DOI: 10.1038/srep18670. View

Bae H, Lee S, Kim T, Kim D, Yang S, Wu H . Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis. Lung Cancer. 2012; 77(3):572-7. DOI: 10.1016/j.lungcan.2012.05.094. View

Fukuoka M, Wu Y, Thongprasert S, Sunpaweravong P, Leong S, Sriuranpong V . Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011; 29(21):2866-74. DOI: 10.1200/JCO.2010.33.4235. View

10.

Hwang J, Lee J, Kim W, Song J, Rho J, Choi C . Clinical Implications of Isolated Bone Failure Without Systemic Disease Progression During EGFR-TKI Treatment. Clin Lung Cancer. 2016; 17(6):573-580.e1. DOI: 10.1016/j.cllc.2016.05.018. View

11.

Beasley M, Brambilla E, Travis W . The 2004 World Health Organization classification of lung tumors. Semin Roentgenol. 2005; 40(2):90-7. DOI: 10.1053/j.ro.2005.01.001. View

12.

Barr S, Thomson S, Buck E, Russo S, Petti F, Sujka-Kwok I . Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions. Clin Exp Metastasis. 2008; 25(6):685-93. PMC: 2471394. DOI: 10.1007/s10585-007-9121-7. View

13.

Gabr A, Goto H, Hanibuchi M, Ogawa H, Kuramoto T, Suzuki M . Erlotinib prevents experimental metastases of human small cell lung cancer cells with no epidermal growth factor receptor expression. Clin Exp Metastasis. 2011; 29(3):207-16. DOI: 10.1007/s10585-011-9443-3. View

14.

Garfield D, Cadranel J, Normanno N . Osteoblastic metastases in non-small cell lung cancer and its possible significance. Lung Cancer. 2008; 60(1):146-147. DOI: 10.1016/j.lungcan.2008.01.006. View

15.

Normanno N, De Luca A, Aldinucci D, Maiello M, Mancino M, DAntonio A . Gefitinib inhibits the ability of human bone marrow stromal cells to induce osteoclast differentiation: implications for the pathogenesis and treatment of bone metastasis. Endocr Relat Cancer. 2005; 12(2):471-82. DOI: 10.1677/erc.1.00956. View

16.

Espinosa J, Gonzalez Del Alba Baamonde A, Rivera Herrero F, Martin E . SEOM guidelines for the treatment of bone metastases from solid tumours. Clin Transl Oncol. 2012; 14(7):505-11. DOI: 10.1007/s12094-012-0832-0. View

17.

Schneider M, Sibilia M, Erben R . The EGFR network in bone biology and pathology. Trends Endocrinol Metab. 2009; 20(10):517-24. DOI: 10.1016/j.tem.2009.06.008. View

18.

Garfield D, Normanno N . Osteoblastosis and activating epidermal growth factor receptor mutations: a relationship?. J Thorac Oncol. 2010; 5(4):415-6. DOI: 10.1097/JTO.0b013e3181d3cd4b. View

19.

Mok T, Yang J, Lam K . Treating patients with EGFR-sensitizing mutations: first line or second line--is there a difference?. J Clin Oncol. 2013; 31(8):1081-8. DOI: 10.1200/JCO.2012.43.0652. View

20.

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