Skip to main content
Top
Published in: Journal of Neuro-Oncology 1/2013

01-01-2013 | Topic Review

EGFR mutation status in brain metastases of non-small cell lung carcinoma

Authors: Fanny Burel-Vandenbos, Damien Ambrosetti, Michael Coutts, Florence Pedeutour

Published in: Journal of Neuro-Oncology | Issue 1/2013

Login to get access

Abstract

Brain metastases are a frequent and grave complication of non-small cell lung carcinoma (NSCLC). The prognosis is generally poor, despite standard therapy based on surgery and radiotherapy. A degree of understanding of the molecular basis of tumors has led to the development of targeted agents with promising initial findings for the treatment of NSCLC. EGFR mutations have been identified which are associated with significant sensitivity to EGFR tyrosine kinase inhibitors (TKI) and correlate with improved outcome in patients with NSCLC who are treated with these agents. The adoption of treatment tailored to the genetic make-up of individual tumors could lead to substantial therapeutic improvements, and such targeted therapy might be considered as a therapeutic option for brain metastases in the future. We review current knowledge about EGFR mutation status in the specific context of brain metastasis: its association with the response of brain metastases to TKI, its prevalence in brain metastases, and the correlation between mutation status in metastases as compared to the corresponding primary lung carcinoma.
Literature
1.
go back to reference Nathoo N, Chahlavi A, Barnett GH, Toms SA (2005) Pathobiology of brain metastases. J Clin Pathol 3:237–242CrossRef Nathoo N, Chahlavi A, Barnett GH, Toms SA (2005) Pathobiology of brain metastases. J Clin Pathol 3:237–242CrossRef
2.
go back to reference Santarelli JG, Sarkissian V, Hou LC, Veeravagu A, Tse V (2007) Molecular events of brain metastasis. Neurosurg Focus 3:E1CrossRef Santarelli JG, Sarkissian V, Hou LC, Veeravagu A, Tse V (2007) Molecular events of brain metastasis. Neurosurg Focus 3:E1CrossRef
3.
go back to reference Eichler AF, Chung E, Kodack DP, Loeffler JS, Fukumura D, Jain RK (2011) The biology of brain metastases-translation to new therapies. Nat Rev Clin Oncol 6:344–356 Eichler AF, Chung E, Kodack DP, Loeffler JS, Fukumura D, Jain RK (2011) The biology of brain metastases-translation to new therapies. Nat Rev Clin Oncol 6:344–356
4.
go back to reference Cox JD, Scott CB, Byhardt RW, Emami B, Russell AH, Fu KK et al (1999) Addition of chemotherapy to radiation therapy alters failure patterns by cell type within non-small cell carcinoma of lung (NSCCL): analysis of radiation therapy oncology group (RTOG) trials. Int J Radiat Oncol Biol Phys 3:505–509CrossRef Cox JD, Scott CB, Byhardt RW, Emami B, Russell AH, Fu KK et al (1999) Addition of chemotherapy to radiation therapy alters failure patterns by cell type within non-small cell carcinoma of lung (NSCCL): analysis of radiation therapy oncology group (RTOG) trials. Int J Radiat Oncol Biol Phys 3:505–509CrossRef
5.
go back to reference Maghfoor I, Perry MC (1998) Lung cancer. In: Hazzard W, Andres R, Bierman E (eds) Principles of geriatric medicine and gerontology, 4th edn. McGraw-Hill, New York Maghfoor I, Perry MC (1998) Lung cancer. In: Hazzard W, Andres R, Bierman E (eds) Principles of geriatric medicine and gerontology, 4th edn. McGraw-Hill, New York
6.
go back to reference Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T et al (1997) Recursive partitioning analysis (RPA) of prognostic factors in three radiation therapy oncology group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 4:745–751CrossRef Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T et al (1997) Recursive partitioning analysis (RPA) of prognostic factors in three radiation therapy oncology group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 4:745–751CrossRef
7.
go back to reference Langer CJ, Mehta MP (2005) Current management of brain metastases, with a focus on systemic options. J Clin Oncol 25:6207–6219CrossRef Langer CJ, Mehta MP (2005) Current management of brain metastases, with a focus on systemic options. J Clin Oncol 25:6207–6219CrossRef
8.
go back to reference Sundstrom JT, Minn H, Lertola KK, Nordman E (1998) Prognosis of patients treated for intracranial metastases with whole-brain irradiation. Ann Med 3:296–299CrossRef Sundstrom JT, Minn H, Lertola KK, Nordman E (1998) Prognosis of patients treated for intracranial metastases with whole-brain irradiation. Ann Med 3:296–299CrossRef
9.
go back to reference Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC et al (2004) Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 9422:1665–1672CrossRef Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC et al (2004) Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 9422:1665–1672CrossRef
10.
go back to reference Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ et al (1990) A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 8:494–500CrossRef Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ et al (1990) A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 8:494–500CrossRef
11.
go back to reference Vecht CJ, Haaxma-Reiche H, Noordijk EM, Padberg GW, Voormolen JH, Hoekstra FH et al (1993) Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol 6:583–590CrossRef Vecht CJ, Haaxma-Reiche H, Noordijk EM, Padberg GW, Voormolen JH, Hoekstra FH et al (1993) Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol 6:583–590CrossRef
12.
go back to reference Ushio Y, Arita N, Hayakawa T, Mogami H, Hasegawa H, Bitoh S et al (1991) Chemotherapy of brain metastases from lung carcinoma: a controlled randomized study. Neurosurgery 2:201–205 Ushio Y, Arita N, Hayakawa T, Mogami H, Hasegawa H, Bitoh S et al (1991) Chemotherapy of brain metastases from lung carcinoma: a controlled randomized study. Neurosurgery 2:201–205
13.
go back to reference Cortes J, Rodriguez J, Aramendia JM, Salgado E, Gurpide A, Garcia-Foncillas J et al (2003) Front-line paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer. Oncology 1:28–35CrossRef Cortes J, Rodriguez J, Aramendia JM, Salgado E, Gurpide A, Garcia-Foncillas J et al (2003) Front-line paclitaxel/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer. Oncology 1:28–35CrossRef
14.
go back to reference Paz-Ares L, Soulieres D, Melezinek I, Moecks J, Keil L, Mok T et al (2010) Clinical outcomes in non-small-cell lung cancer patients with EGFR mutations: pooled analysis. J Cell Mol Med 1–2:51–69CrossRef Paz-Ares L, Soulieres D, Melezinek I, Moecks J, Keil L, Mok T et al (2010) Clinical outcomes in non-small-cell lung cancer patients with EGFR mutations: pooled analysis. J Cell Mol Med 1–2:51–69CrossRef
15.
go back to reference Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C et al (2009) Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 10:958–967CrossRef Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C et al (2009) Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 10:958–967CrossRef
16.
go back to reference Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 21:2129–2139CrossRef Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 21:2129–2139CrossRef
17.
go back to reference Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 10:947–957CrossRef Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 10:947–957CrossRef
18.
go back to reference Sharma SV, Bell DW, Settleman J, Haber DA (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 3:169–181CrossRef Sharma SV, Bell DW, Settleman J, Haber DA (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 3:169–181CrossRef
19.
go back to reference Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba II et al (2005) Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 5:339–346CrossRef Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba II et al (2005) Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 5:339–346CrossRef
20.
go back to reference Tanaka T, Matsuoka M, Sutani A, Gemma A, Maemondo M, Inoue A et al (2010) Frequency of and variables associated with the EGFR mutation and its subtypes. Int J Cancer 3:651–655CrossRef Tanaka T, Matsuoka M, Sutani A, Gemma A, Maemondo M, Inoue A et al (2010) Frequency of and variables associated with the EGFR mutation and its subtypes. Int J Cancer 3:651–655CrossRef
21.
go back to reference Sanders HR, Albitar M (2010) Somatic mutations of signaling genes in non-small-cell lung cancer. Cancer Genet Cytogenet 1:7–15CrossRef Sanders HR, Albitar M (2010) Somatic mutations of signaling genes in non-small-cell lung cancer. Cancer Genet Cytogenet 1:7–15CrossRef
22.
go back to reference Sartori G, Cavazza A, Sgambato A, Marchioni A, Barbieri F, Longo L et al (2009) EGFR and K-ras mutations along the spectrum of pulmonary epithelial tumors of the lung and elaboration of a combined clinicopathologic and molecular scoring system to predict clinical responsiveness to EGFR inhibitors. Am J Clin Pathol 4:478–489CrossRef Sartori G, Cavazza A, Sgambato A, Marchioni A, Barbieri F, Longo L et al (2009) EGFR and K-ras mutations along the spectrum of pulmonary epithelial tumors of the lung and elaboration of a combined clinicopathologic and molecular scoring system to predict clinical responsiveness to EGFR inhibitors. Am J Clin Pathol 4:478–489CrossRef
23.
go back to reference Gately K, O’Flaherty J, Cappuzzo F, Pirker R, Kerr K, O’Byrne K (2012) The role of the molecular footprint of EGFR in tailoring treatment decisions in NSCLC. J Clin Pathol 1:1–7CrossRef Gately K, O’Flaherty J, Cappuzzo F, Pirker R, Kerr K, O’Byrne K (2012) The role of the molecular footprint of EGFR in tailoring treatment decisions in NSCLC. J Clin Pathol 1:1–7CrossRef
24.
go back to reference Pao W, Ladanyi M (2007) Epidermal growth factor receptor mutation testing in lung cancer: searching for the ideal method. Clin Cancer Res 17:4954–4955CrossRef Pao W, Ladanyi M (2007) Epidermal growth factor receptor mutation testing in lung cancer: searching for the ideal method. Clin Cancer Res 17:4954–4955CrossRef
25.
go back to reference Matsumoto S, Takahashi K, Iwakawa R, Matsuno Y, Nakanishi Y, Kohno T et al (2006) Frequent EGFR mutations in brain metastases of lung adenocarcinoma. Int J Cancer 6:1491–1494CrossRef Matsumoto S, Takahashi K, Iwakawa R, Matsuno Y, Nakanishi Y, Kohno T et al (2006) Frequent EGFR mutations in brain metastases of lung adenocarcinoma. Int J Cancer 6:1491–1494CrossRef
26.
go back to reference Gow CH, Chang YL, Hsu YC, Tsai MF, Wu CT, Yu CJ et al (2009) Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer. Ann Oncol 4:696–702CrossRef Gow CH, Chang YL, Hsu YC, Tsai MF, Wu CT, Yu CJ et al (2009) Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer. Ann Oncol 4:696–702CrossRef
27.
go back to reference Huang SF, Liu HP, Li LH, Ku YC, Fu YN, Tsai HY et al (2004) High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan. Clin Cancer Res 24:8195–8203CrossRef Huang SF, Liu HP, Li LH, Ku YC, Fu YN, Tsai HY et al (2004) High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan. Clin Cancer Res 24:8195–8203CrossRef
28.
go back to reference Wu YL, Zhong WZ, Li LY, Zhang XT, Zhang L, Zhou CC et al (2007) Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China. J Thorac Oncol 5:430–439CrossRef Wu YL, Zhong WZ, Li LY, Zhang XT, Zhang L, Zhou CC et al (2007) Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China. J Thorac Oncol 5:430–439CrossRef
29.
go back to reference Cortot AB, Italiano A, Burel-Vandenbos F, Martel-Planche G, Hainaut P (2010) KRAS mutation status in primary nonsmall cell lung cancer and matched metastases. Cancer 11:2682–2687CrossRef Cortot AB, Italiano A, Burel-Vandenbos F, Martel-Planche G, Hainaut P (2010) KRAS mutation status in primary nonsmall cell lung cancer and matched metastases. Cancer 11:2682–2687CrossRef
30.
go back to reference Daniele L, Cassoni P, Bacillo E, Cappia S, Righi L, Volante M et al (2009) Epidermal growth factor receptor gene in primary tumor and metastatic sites from non-small cell lung cancer. J Thorac Oncol 6:684–688CrossRef Daniele L, Cassoni P, Bacillo E, Cappia S, Righi L, Volante M et al (2009) Epidermal growth factor receptor gene in primary tumor and metastatic sites from non-small cell lung cancer. J Thorac Oncol 6:684–688CrossRef
31.
go back to reference Sun M, Behrens C, Feng L, Ozburn N, Tang X, Yin G et al (2009) HER family receptor abnormalities in lung cancer brain metastases and corresponding primary tumors. Clin Cancer Res 15:4829–4837PubMedCrossRef Sun M, Behrens C, Feng L, Ozburn N, Tang X, Yin G et al (2009) HER family receptor abnormalities in lung cancer brain metastases and corresponding primary tumors. Clin Cancer Res 15:4829–4837PubMedCrossRef
32.
go back to reference Gazdar AF (2009) Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene S24-31 Gazdar AF (2009) Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene S24-31
33.
go back to reference Marchetti A, Martella C, Felicioni L, Barassi F, Salvatore S, Chella A et al (2005) EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol 4:857–865CrossRef Marchetti A, Martella C, Felicioni L, Barassi F, Salvatore S, Chella A et al (2005) EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol 4:857–865CrossRef
34.
go back to reference Li Z, Guo H (2011) The retrospective analysis of the frequency of EGFR mutations and efficacy of gefitinib in NSCLC patients with brain metastases. J Clin Oncol 29 (Suppl abstr e18065) Li Z, Guo H (2011) The retrospective analysis of the frequency of EGFR mutations and efficacy of gefitinib in NSCLC patients with brain metastases. J Clin Oncol 29 (Suppl abstr e18065)
35.
go back to reference Eichler AF, Kahle KT, Wang DL, Joshi VA, Willers H, Engelman JA et al (2010) EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer. Neuro Oncol 11:1193–1199CrossRef Eichler AF, Kahle KT, Wang DL, Joshi VA, Willers H, Engelman JA et al (2010) EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer. Neuro Oncol 11:1193–1199CrossRef
36.
go back to reference Heon S, Yeap BY, Britt GJ, Costa DB, Rabin MS, Jackman DM et al (2010) Development of central nervous system metastases in patients with advanced non-small cell lung cancer and somatic EGFR mutations treated with gefitinib or erlotinib. Clin Cancer Res 23:5873–5882CrossRef Heon S, Yeap BY, Britt GJ, Costa DB, Rabin MS, Jackman DM et al (2010) Development of central nervous system metastases in patients with advanced non-small cell lung cancer and somatic EGFR mutations treated with gefitinib or erlotinib. Clin Cancer Res 23:5873–5882CrossRef
37.
go back to reference Sekine A, Kato T, Hagiwara E, Shinohara T, Komagata T, Iwasawa T et al (2012) Metastatic brain tumors from non-small cell lung cancer with EGFR mutations: distinguishing influence of exon 19 deletion on radiographic features. Lung Cancer 1:64–69CrossRef Sekine A, Kato T, Hagiwara E, Shinohara T, Komagata T, Iwasawa T et al (2012) Metastatic brain tumors from non-small cell lung cancer with EGFR mutations: distinguishing influence of exon 19 deletion on radiographic features. Lung Cancer 1:64–69CrossRef
38.
go back to reference Heimberger AB, Learn CA, Archer GE, McLendon RE, Chewning TA, Tuck FL et al (2002) Brain tumors in mice are susceptible to blockade of epidermal growth factor receptor (EGFR) with the oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (iressa). Clin Cancer Res 11:3496–3502 Heimberger AB, Learn CA, Archer GE, McLendon RE, Chewning TA, Tuck FL et al (2002) Brain tumors in mice are susceptible to blockade of epidermal growth factor receptor (EGFR) with the oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (iressa). Clin Cancer Res 11:3496–3502
39.
go back to reference Gounant V, Wislez M, Poulot V, Khalil A, Lavole A, Cadranel J et al (2007) Subsequent brain metastasis responses to epidermal growth factor receptor tyrosine kinase inhibitors in a patient with non-small-cell lung cancer. Lung Cancer 3:425–428CrossRef Gounant V, Wislez M, Poulot V, Khalil A, Lavole A, Cadranel J et al (2007) Subsequent brain metastasis responses to epidermal growth factor receptor tyrosine kinase inhibitors in a patient with non-small-cell lung cancer. Lung Cancer 3:425–428CrossRef
40.
go back to reference Popat S, Hughes S, Papadopoulos P, Wilkins A, Moore S, Priest K et al (2007) Recurrent responses to non-small cell lung cancer brain metastases with erlotinib. Lung Cancer 1:135–137CrossRef Popat S, Hughes S, Papadopoulos P, Wilkins A, Moore S, Priest K et al (2007) Recurrent responses to non-small cell lung cancer brain metastases with erlotinib. Lung Cancer 1:135–137CrossRef
41.
go back to reference Fekrazad MH, Ravindranathan M, Jones DV Jr (2007) Response of intracranial metastases to erlotinib therapy. J Clin Oncol 31:5024–5026CrossRef Fekrazad MH, Ravindranathan M, Jones DV Jr (2007) Response of intracranial metastases to erlotinib therapy. J Clin Oncol 31:5024–5026CrossRef
42.
go back to reference Cappuzzo F, Ardizzoni A, Soto-Parra H, Gridelli C, Maione P, Tiseo M et al (2003) Epidermal growth factor receptor targeted therapy by ZD 1839 (Iressa) in patients with brain metastases from non-small cell lung cancer (NSCLC). Lung Cancer 2:227–231CrossRef Cappuzzo F, Ardizzoni A, Soto-Parra H, Gridelli C, Maione P, Tiseo M et al (2003) Epidermal growth factor receptor targeted therapy by ZD 1839 (Iressa) in patients with brain metastases from non-small cell lung cancer (NSCLC). Lung Cancer 2:227–231CrossRef
43.
go back to reference Shimato S, Mitsudomi T, Kosaka T, Yatabe Y, Wakabayashi T, Mizuno M et al (2006) EGFR mutations in patients with brain metastases from lung cancer: association with the efficacy of gefitinib. Neuro Oncol 2:137–144CrossRef Shimato S, Mitsudomi T, Kosaka T, Yatabe Y, Wakabayashi T, Mizuno M et al (2006) EGFR mutations in patients with brain metastases from lung cancer: association with the efficacy of gefitinib. Neuro Oncol 2:137–144CrossRef
44.
go back to reference Namba Y, Kijima T, Yokota S, Niinaka M, Kawamura S, Iwasaki T et al (2004) Gefitinib in patients with brain metastases from non-small-cell lung cancer: review of 15 clinical cases. Clin Lung Cancer 2:123–128CrossRef Namba Y, Kijima T, Yokota S, Niinaka M, Kawamura S, Iwasaki T et al (2004) Gefitinib in patients with brain metastases from non-small-cell lung cancer: review of 15 clinical cases. Clin Lung Cancer 2:123–128CrossRef
45.
go back to reference Jamal-Hanjani M, Spicer J (2012) Epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of epidermal growth factor receptor-mutant non-small cell lung cancer metastatic to the brain. Clin Cancer Res 4:938–944CrossRef Jamal-Hanjani M, Spicer J (2012) Epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of epidermal growth factor receptor-mutant non-small cell lung cancer metastatic to the brain. Clin Cancer Res 4:938–944CrossRef
46.
go back to reference Wu C, Li YL, Wang ZM, Li Z, Zhang TX, Wei Z (2007) Gefitinib as palliative therapy for lung adenocarcinoma metastatic to the brain. Lung Cancer 3:359–364CrossRef Wu C, Li YL, Wang ZM, Li Z, Zhang TX, Wei Z (2007) Gefitinib as palliative therapy for lung adenocarcinoma metastatic to the brain. Lung Cancer 3:359–364CrossRef
47.
go back to reference Kim JE, Lee DH, Choi Y, Yoon DH, Kim SW, Suh C et al (2009) Epidermal growth factor receptor tyrosine kinase inhibitors as a first-line therapy for never-smokers with adenocarcinoma of the lung having asymptomatic synchronous brain metastasis. Lung Cancer 3:351–354CrossRef Kim JE, Lee DH, Choi Y, Yoon DH, Kim SW, Suh C et al (2009) Epidermal growth factor receptor tyrosine kinase inhibitors as a first-line therapy for never-smokers with adenocarcinoma of the lung having asymptomatic synchronous brain metastasis. Lung Cancer 3:351–354CrossRef
48.
go back to reference Ceresoli GL, Cappuzzo F, Gregorc V, Bartolini S, Crino L, Villa E (2004) Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial. Ann Oncol 7:1042–1047CrossRef Ceresoli GL, Cappuzzo F, Gregorc V, Bartolini S, Crino L, Villa E (2004) Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial. Ann Oncol 7:1042–1047CrossRef
49.
go back to reference Hotta K, Kiura K, Ueoka H, Tabata M, Fujiwara K, Kozuki T et al (2004) Effect of gefitinib (‘Iressa’, ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer. Lung Cancer 2:255–261CrossRef Hotta K, Kiura K, Ueoka H, Tabata M, Fujiwara K, Kozuki T et al (2004) Effect of gefitinib (‘Iressa’, ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer. Lung Cancer 2:255–261CrossRef
50.
go back to reference Porta R, Sanchez-Torres JM, Paz-Ares L, Massuti B, Reguart N, Mayo C et al (2011) Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation. Eur Respir J 3:624–631CrossRef Porta R, Sanchez-Torres JM, Paz-Ares L, Massuti B, Reguart N, Mayo C et al (2011) Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation. Eur Respir J 3:624–631CrossRef
51.
go back to reference Omuro AM, Kris MG, Miller VA, Franceschi E, Shah N, Milton DT et al (2005) High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib. Cancer 11:2344–2348CrossRef Omuro AM, Kris MG, Miller VA, Franceschi E, Shah N, Milton DT et al (2005) High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to gefitinib. Cancer 11:2344–2348CrossRef
52.
go back to reference Elmeliegy MA, Carcaboso AM, Tagen M, Bai F, Stewart CF (2011) Role of ATP-binding cassette and solute carrier transporters in erlotinib CNS penetration and intracellular accumulation. Clin Cancer Res 1:89–99CrossRef Elmeliegy MA, Carcaboso AM, Tagen M, Bai F, Stewart CF (2011) Role of ATP-binding cassette and solute carrier transporters in erlotinib CNS penetration and intracellular accumulation. Clin Cancer Res 1:89–99CrossRef
53.
go back to reference Weber B, Winterdahl M, Memon A, Sorensen BS, Keiding S, Sorensen L et al (2011) Erlotinib accumulation in brain metastases from non-small cell lung cancer: visualization by positron emission tomography in a patient harboring a mutation in the epidermal growth factor receptor. J Thorac Oncol 7:1287–1289CrossRef Weber B, Winterdahl M, Memon A, Sorensen BS, Keiding S, Sorensen L et al (2011) Erlotinib accumulation in brain metastases from non-small cell lung cancer: visualization by positron emission tomography in a patient harboring a mutation in the epidermal growth factor receptor. J Thorac Oncol 7:1287–1289CrossRef
54.
go back to reference Jackman DM, Holmes AJ, Lindeman N, Wen PY, Kesari S, Borras AM et al (2006) Response and resistance in a non-small-cell lung cancer patient with an epidermal growth factor receptor mutation and leptomeningeal metastases treated with high-dose gefitinib. J Clin Oncol 27:4517–4520CrossRef Jackman DM, Holmes AJ, Lindeman N, Wen PY, Kesari S, Borras AM et al (2006) Response and resistance in a non-small-cell lung cancer patient with an epidermal growth factor receptor mutation and leptomeningeal metastases treated with high-dose gefitinib. J Clin Oncol 27:4517–4520CrossRef
55.
go back to reference Clarke JL, Pao W, Wu N, Miller VA, Lassman AB (2010) High dose weekly erlotinib achieves therapeutic concentrations in CSF and is effective in leptomeningeal metastases from epidermal growth factor receptor mutant lung cancer. J Neurooncol 2:283–286CrossRef Clarke JL, Pao W, Wu N, Miller VA, Lassman AB (2010) High dose weekly erlotinib achieves therapeutic concentrations in CSF and is effective in leptomeningeal metastases from epidermal growth factor receptor mutant lung cancer. J Neurooncol 2:283–286CrossRef
56.
go back to reference Masuda T, Hattori N, Hamada A, Iwamoto H, Ohshimo S, Kanehara M et al (2011) Erlotinib efficacy and cerebrospinal fluid concentration in patients with lung adenocarcinoma developing leptomeningeal metastases during gefitinib therapy. Cancer Chemother Pharmacol 6:1465–1469CrossRef Masuda T, Hattori N, Hamada A, Iwamoto H, Ohshimo S, Kanehara M et al (2011) Erlotinib efficacy and cerebrospinal fluid concentration in patients with lung adenocarcinoma developing leptomeningeal metastases during gefitinib therapy. Cancer Chemother Pharmacol 6:1465–1469CrossRef
57.
go back to reference Togashi Y, Masago K, Fukudo M, Tsuchido Y, Okuda C, Kim YH et al (2011) Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation. Cancer Chemother Pharmacol 4:1089–1092CrossRef Togashi Y, Masago K, Fukudo M, Tsuchido Y, Okuda C, Kim YH et al (2011) Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation. Cancer Chemother Pharmacol 4:1089–1092CrossRef
58.
go back to reference Hata A, Kaji R, Fujita S, Katakami N (2011) High-dose erlotinib for refractory brain metastases in a patient with relapsed non-small cell lung cancer. J Thorac Oncol 3:653–654CrossRef Hata A, Kaji R, Fujita S, Katakami N (2011) High-dose erlotinib for refractory brain metastases in a patient with relapsed non-small cell lung cancer. J Thorac Oncol 3:653–654CrossRef
59.
go back to reference Grommes C, Oxnard GR, Kris MG, Miller VA, Pao W, Holodny AI et al (2011) “Pulsatile” high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. Neuro Oncol 12:1364–1369CrossRef Grommes C, Oxnard GR, Kris MG, Miller VA, Pao W, Holodny AI et al (2011) “Pulsatile” high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. Neuro Oncol 12:1364–1369CrossRef
60.
go back to reference Dhruva N, Socinski MA (2009) Carcinomatous meningitis in non-small-cell lung cancer: response to high-dose erlotinib. J Clin Oncol 22:e31–e32CrossRef Dhruva N, Socinski MA (2009) Carcinomatous meningitis in non-small-cell lung cancer: response to high-dose erlotinib. J Clin Oncol 22:e31–e32CrossRef
61.
go back to reference Xu Y, Lin N, Yu Y, Fang L, Sun X and Jiang H (2011) Cerebrospinal fluid concentration of gefitinib in patients with central nervous system metastases of non-small cell lung cancer. J Thorac Oncol: S659–S660 Xu Y, Lin N, Yu Y, Fang L, Sun X and Jiang H (2011) Cerebrospinal fluid concentration of gefitinib in patients with central nervous system metastases of non-small cell lung cancer. J Thorac Oncol: S659–S660
62.
go back to reference Morris PG, Reiner AS, Szenberg OR, Clarke JL, Panageas KS, Perez HR et al (2012) Leptomeningeal metastasis from non-small cell lung cancer: survival and the impact of whole brain radiotherapy. J Thorac Oncol 2:382–385CrossRef Morris PG, Reiner AS, Szenberg OR, Clarke JL, Panageas KS, Perez HR et al (2012) Leptomeningeal metastasis from non-small cell lung cancer: survival and the impact of whole brain radiotherapy. J Thorac Oncol 2:382–385CrossRef
63.
go back to reference Yi HG, Kim HJ, Kim YJ, Han SW, Oh DY, Lee SH et al (2009) Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for leptomeningeal metastasis from non-small cell lung cancer patients with sensitive EGFR mutation or other predictive factors of good response for EGFR TKI. Lung Cancer 1:80–84CrossRef Yi HG, Kim HJ, Kim YJ, Han SW, Oh DY, Lee SH et al (2009) Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for leptomeningeal metastasis from non-small cell lung cancer patients with sensitive EGFR mutation or other predictive factors of good response for EGFR TKI. Lung Cancer 1:80–84CrossRef
64.
go back to reference de Vries NA, Buckle T, Zhao J, Beijnen JH, Schellens JH, van Tellingen O (2012) Restricted brain penetration of the tyrosine kinase inhibitor erlotinib due to the drug transporters P-gp and BCRP. Invest New Drugs 2:443–449CrossRef de Vries NA, Buckle T, Zhao J, Beijnen JH, Schellens JH, van Tellingen O (2012) Restricted brain penetration of the tyrosine kinase inhibitor erlotinib due to the drug transporters P-gp and BCRP. Invest New Drugs 2:443–449CrossRef
65.
go back to reference Fukuhara T, Saijo Y, Sakakibara T, Inoue A, Morikawa N, Kanamori M et al (2008) Successful treatment of carcinomatous meningitis with gefitinib in a patient with lung adenocarcinoma harboring a mutated EGF receptor gene. Tohoku J Exp Med 4:359–363CrossRef Fukuhara T, Saijo Y, Sakakibara T, Inoue A, Morikawa N, Kanamori M et al (2008) Successful treatment of carcinomatous meningitis with gefitinib in a patient with lung adenocarcinoma harboring a mutated EGF receptor gene. Tohoku J Exp Med 4:359–363CrossRef
66.
go back to reference Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF et al (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 3:e73CrossRef Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF et al (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 3:e73CrossRef
67.
go back to reference Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO et al (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 5827:1039–1043CrossRef Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO et al (2007) MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 5827:1039–1043CrossRef
68.
go back to reference Bean J, Riely GJ, Balak M, Marks JL, Ladanyi M, Miller VA et al (2008) Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma. Clin Cancer Res 22:7519–7525CrossRef Bean J, Riely GJ, Balak M, Marks JL, Ladanyi M, Miller VA et al (2008) Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma. Clin Cancer Res 22:7519–7525CrossRef
69.
go back to reference Balak MN, Gong Y, Riely GJ, Somwar R, Li AR, Zakowski MF et al (2006) Novel D761Y and common secondary T790 M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res 21:6494–6501CrossRef Balak MN, Gong Y, Riely GJ, Somwar R, Li AR, Zakowski MF et al (2006) Novel D761Y and common secondary T790 M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res 21:6494–6501CrossRef
70.
go back to reference Guix M, Faber AC, Wang SE, Olivares MG, Song Y, Qu S et al (2008) Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J Clin Invest 7:2609–2619 Guix M, Faber AC, Wang SE, Olivares MG, Song Y, Qu S et al (2008) Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J Clin Invest 7:2609–2619
71.
go back to reference Katayama T, Shimizu J, Suda K, Onozato R, Fukui T, Ito S et al (2009) Efficacy of erlotinib for brain and leptomeningeal metastases in patients with lung adenocarcinoma who showed initial good response to gefitinib. J Thorac Oncol 11:1415–1419CrossRef Katayama T, Shimizu J, Suda K, Onozato R, Fukui T, Ito S et al (2009) Efficacy of erlotinib for brain and leptomeningeal metastases in patients with lung adenocarcinoma who showed initial good response to gefitinib. J Thorac Oncol 11:1415–1419CrossRef
72.
go back to reference Benedettini E, Sholl LM, Peyton M, Reilly J, Ware C, Davis L et al (2010) Met activation in non-small cell lung cancer is associated with de novo resistance to EGFR inhibitors and the development of brain metastasis. Am J Pathol 1:415–423CrossRef Benedettini E, Sholl LM, Peyton M, Reilly J, Ware C, Davis L et al (2010) Met activation in non-small cell lung cancer is associated with de novo resistance to EGFR inhibitors and the development of brain metastasis. Am J Pathol 1:415–423CrossRef
73.
go back to reference Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 5676:1497–1500CrossRef Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 5676:1497–1500CrossRef
74.
go back to reference Italiano A, Vandenbos FB, Otto J, Mouroux J, Fontaine D, Marcy PY et al (2006) Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors. Ann Oncol 6:981–985CrossRef Italiano A, Vandenbos FB, Otto J, Mouroux J, Fontaine D, Marcy PY et al (2006) Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors. Ann Oncol 6:981–985CrossRef
75.
go back to reference Gomez-Roca C, Raynaud CM, Penault-Llorca F, Mercier O, Commo F, Morat L et al (2009) Differential expression of biomarkers in primary non-small cell lung cancer and metastatic sites. J Thorac Oncol 10:1212–1220CrossRef Gomez-Roca C, Raynaud CM, Penault-Llorca F, Mercier O, Commo F, Morat L et al (2009) Differential expression of biomarkers in primary non-small cell lung cancer and metastatic sites. J Thorac Oncol 10:1212–1220CrossRef
76.
go back to reference Sun L, Zhang Q, Luan H, Zhan Z, Wang C, Sun B (2011) Comparison of KRAS and EGFR gene status between primary non-small cell lung cancer and local lymph node metastases: implications for clinical practice. J Exp Clin Cancer Res 30:30 Sun L, Zhang Q, Luan H, Zhan Z, Wang C, Sun B (2011) Comparison of KRAS and EGFR gene status between primary non-small cell lung cancer and local lymph node metastases: implications for clinical practice. J Exp Clin Cancer Res 30:30
77.
go back to reference Park S, Holmes-Tisch AJ, Cho EY, Shim YM, Kim J, Kim HS et al (2009) Discordance of molecular biomarkers associated with epidermal growth factor receptor pathway between primary tumors and lymph node metastasis in non-small cell lung cancer. J Thorac Oncol 7:809–815CrossRef Park S, Holmes-Tisch AJ, Cho EY, Shim YM, Kim J, Kim HS et al (2009) Discordance of molecular biomarkers associated with epidermal growth factor receptor pathway between primary tumors and lymph node metastasis in non-small cell lung cancer. J Thorac Oncol 7:809–815CrossRef
78.
go back to reference Chang YL, Wu CT, Shih JY, Lee YC (2011) Comparison of p53 and epidermal growth factor receptor gene status between primary tumors and lymph node metastases in non-small cell lung cancers. Ann Surg Oncol 2:543–550CrossRef Chang YL, Wu CT, Shih JY, Lee YC (2011) Comparison of p53 and epidermal growth factor receptor gene status between primary tumors and lymph node metastases in non-small cell lung cancers. Ann Surg Oncol 2:543–550CrossRef
79.
go back to reference Han CB, Ma JT, Li F, Zhao JZ, Jing W, Zhou Y et al (2012) EGFR and KRAS mutations and altered c-Met gene copy numbers in primary non-small cell lung cancer and associated stage N2 lymph node-metastasis. Cancer Lett 1:63–72CrossRef Han CB, Ma JT, Li F, Zhao JZ, Jing W, Zhou Y et al (2012) EGFR and KRAS mutations and altered c-Met gene copy numbers in primary non-small cell lung cancer and associated stage N2 lymph node-metastasis. Cancer Lett 1:63–72CrossRef
80.
go back to reference Han HS, Eom DW, Kim JH, Kim KH, Shin HM, An JY et al (2011) EGFR mutation status in primary lung adenocarcinomas and corresponding metastatic lesions: discordance in pleural metastases. Clin Lung Cancer 6:380–386CrossRef Han HS, Eom DW, Kim JH, Kim KH, Shin HM, An JY et al (2011) EGFR mutation status in primary lung adenocarcinomas and corresponding metastatic lesions: discordance in pleural metastases. Clin Lung Cancer 6:380–386CrossRef
81.
go back to reference Schmid K, Oehl N, Wrba F, Pirker R, Pirker C, Filipits M (2009) EGFR/KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding locoregional lymph node metastases. Clin Cancer Res 14:4554–4560CrossRef Schmid K, Oehl N, Wrba F, Pirker R, Pirker C, Filipits M (2009) EGFR/KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding locoregional lymph node metastases. Clin Cancer Res 14:4554–4560CrossRef
82.
go back to reference Munfus-McCray D, Harada S, Adams C, Askin F, Clark D, Gabrielson E et al (2011) EGFR and KRAS mutations in metastatic lung adenocarcinomas. Hum Pathol 10:1447–1453CrossRef Munfus-McCray D, Harada S, Adams C, Askin F, Clark D, Gabrielson E et al (2011) EGFR and KRAS mutations in metastatic lung adenocarcinomas. Hum Pathol 10:1447–1453CrossRef
83.
go back to reference Kalikaki A, Koutsopoulos A, Trypaki M, Souglakos J, Stathopoulos E, Georgoulias V et al (2008) Comparison of EGFR and K-RAS gene status between primary tumours and corresponding metastases in NSCLC. Br J Cancer 6:923–929CrossRef Kalikaki A, Koutsopoulos A, Trypaki M, Souglakos J, Stathopoulos E, Georgoulias V et al (2008) Comparison of EGFR and K-RAS gene status between primary tumours and corresponding metastases in NSCLC. Br J Cancer 6:923–929CrossRef
84.
go back to reference Fang Q, Zhang L, Wang S, Ou W (2011) Discordance of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in non-small cell lung cancer. Zhongguo Fei Ai Za Zhi 6:518–522 Fang Q, Zhang L, Wang S, Ou W (2011) Discordance of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in non-small cell lung cancer. Zhongguo Fei Ai Za Zhi 6:518–522
85.
go back to reference Han C, Zou H, Ma J, Zhou Y, Zhao J (2010) Comparison of EGFR and KRAS status between primary non-small cell lung cancer and corresponding metastases: a systematic review and meta-analysis. Zhongguo Fei Ai Za Zhi 9:882–891 Han C, Zou H, Ma J, Zhou Y, Zhao J (2010) Comparison of EGFR and KRAS status between primary non-small cell lung cancer and corresponding metastases: a systematic review and meta-analysis. Zhongguo Fei Ai Za Zhi 9:882–891
86.
go back to reference Ruppert AM, Beau-Faller M, Neuville A, Guerin E, Voegeli AC, Mennecier B et al (2009) EGFR-TKI and lung adenocarcinoma with CNS relapse: interest of molecular follow-up. Eur Respir J 2:436–440 Ruppert AM, Beau-Faller M, Neuville A, Guerin E, Voegeli AC, Mennecier B et al (2009) EGFR-TKI and lung adenocarcinoma with CNS relapse: interest of molecular follow-up. Eur Respir J 2:436–440
Metadata
Title
EGFR mutation status in brain metastases of non-small cell lung carcinoma
Authors
Fanny Burel-Vandenbos
Damien Ambrosetti
Michael Coutts
Florence Pedeutour
Publication date
01-01-2013
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2013
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-012-0990-5

Other articles of this Issue 1/2013

Journal of Neuro-Oncology 1/2013 Go to the issue