Skip to main content
Top
Published in: BMC Pulmonary Medicine 1/2018

Open Access 01-12-2018 | Research article

Erlotinib versus gefitinib for brain metastases in Asian patients with exon 19 EGFR-mutant lung adenocarcinoma: a retrospective, multicenter study

Authors: Ye Jiang, Jing Zhang, Juanjuan Huang, Bo Xu, Ning Li, Lei Cao, Mingdong Zhao

Published in: BMC Pulmonary Medicine | Issue 1/2018

Login to get access

Abstract

Background

The purpose of this study was to compare clinical outcomes of Erlotinib versus Gefitinib in the treatment of Asian patients with exon 19 EGFR-mutant lung adenocarcinoma and newly diagnosed brain metastases.

Methods

Consecutive Asian patients with exon 19 EGFR-mutant lung adenocarcinoma and newly diagnosed brain metastases were identified and initially received peroral administration of 150 mg/d erlotinib or 250 mg/d gefitinib during 2009–2015. Overall survival (OS) was the primary endpoint. Progression-free survival (PFS) was the second endpoint.

Results

The cohort consisted of 227 Asian patients (erlotinib-treated cohort: n = 112, mean age = 58.5 years [SD: 20.13]; gefitinib-treated cohort: n = 115, mean age = 58.4 years [SD: 19.52]). In a multivariate analysis controlling for age, sex and time span of smoking history, significant difference was detected in the 36-month OS between erlotinib and gefitinib groups (58.3% vs. 49.1%, p = 0.012). There was also significant difference in the 36-month PFS between erlotinib and gefitinib groups (64% vs. 53%, p = 0.013).

Conclusion

For Asian patients with exon 19 EGFR-mutant lung adenocarcinoma and brain metastases, erlotinib was associated with a significantly longer OS and a more prolonged PFS and compared with gefitinib.
Literature
1.
go back to reference Yomo S, Oda K. Impacts of EGFR-mutation status and EGFR-TKI on the efficacy of stereotactic radiosurgery for brain metastases from non-small cell lung adenocarcinoma: a retrospective analysis of 133 consecutive patients. Lung Cancer. 2018;119:120–6.CrossRef Yomo S, Oda K. Impacts of EGFR-mutation status and EGFR-TKI on the efficacy of stereotactic radiosurgery for brain metastases from non-small cell lung adenocarcinoma: a retrospective analysis of 133 consecutive patients. Lung Cancer. 2018;119:120–6.CrossRef
2.
go back to reference Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, et al. Randomized phase III study comparing Gefitinib with Erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016;34(27):3248.CrossRef Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, et al. Randomized phase III study comparing Gefitinib with Erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016;34(27):3248.CrossRef
3.
go back to reference Ostoros G, Sarosi V, Mandoky L, Pinter F, Schwab R, Petak I, et al. Effectiveness of erlotinib in lung adenocarcinomas with classic and alternative EGFR mutations detected by Roche 454 GS-FLX next-generation sequencing (NGS). J Clin Oncol. 2013;31(15). Ostoros G, Sarosi V, Mandoky L, Pinter F, Schwab R, Petak I, et al. Effectiveness of erlotinib in lung adenocarcinomas with classic and alternative EGFR mutations detected by Roche 454 GS-FLX next-generation sequencing (NGS). J Clin Oncol. 2013;31(15).
4.
go back to reference Lee CN, Chen HY, Liu HE. Favorable response to Erlotinib in a lung adenocarcinoma with both epidermal growth factor receptor exon 19 deletion and K-ras G13D mutations. J Clin Oncol. 2010;28(7):E111–E2.CrossRef Lee CN, Chen HY, Liu HE. Favorable response to Erlotinib in a lung adenocarcinoma with both epidermal growth factor receptor exon 19 deletion and K-ras G13D mutations. J Clin Oncol. 2010;28(7):E111–E2.CrossRef
5.
go back to reference Fan WC, Yu CJ, Tsai CM, Huang MS, Lai CL, Hsia TC, et al. Different efficacies of Erlotinib and Gefitinib in Taiwanese patients with advanced non-small cell lung Cancer a retrospective multicenter study. J Thorac Oncol. 2011;6(1):148–55.CrossRef Fan WC, Yu CJ, Tsai CM, Huang MS, Lai CL, Hsia TC, et al. Different efficacies of Erlotinib and Gefitinib in Taiwanese patients with advanced non-small cell lung Cancer a retrospective multicenter study. J Thorac Oncol. 2011;6(1):148–55.CrossRef
6.
go back to reference Janjigian YY, Park BJ, Kris MG, Miller VA, Riely GJ, Zheng J, et al. Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR) mutations. J Clin Oncol. 2009;27(15). Janjigian YY, Park BJ, Kris MG, Miller VA, Riely GJ, Zheng J, et al. Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor epidermal growth factor receptor (EGFR) mutations. J Clin Oncol. 2009;27(15).
8.
go back to reference Gerber NK, Yamada Y, Rimner A, Shi WJ, Riely GJ, Beal K, et al. Erlotinib versus radiation therapy for brain metastases in patients with EGFR-mutant lung adenocarcinoma. Int J Radiat Oncol Biol Phys. 2014;89(2):322–9.CrossRef Gerber NK, Yamada Y, Rimner A, Shi WJ, Riely GJ, Beal K, et al. Erlotinib versus radiation therapy for brain metastases in patients with EGFR-mutant lung adenocarcinoma. Int J Radiat Oncol Biol Phys. 2014;89(2):322–9.CrossRef
9.
go back to reference Zhuang H, Yuan Z, Wang J, Zhao L, Wang P. Phase II study of WBRT with or without concurrent Erlotinib for patients with brain metastases from lung adenocarcinoma. Int J Radiat Oncol Biol Phys. 2012;84(3):S102.CrossRef Zhuang H, Yuan Z, Wang J, Zhao L, Wang P. Phase II study of WBRT with or without concurrent Erlotinib for patients with brain metastases from lung adenocarcinoma. Int J Radiat Oncol Biol Phys. 2012;84(3):S102.CrossRef
10.
go back to reference Zhuang HQ, Yuan ZY, Wang J, Zhao LJ, Pang QS, Wang P. Phase II study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma. Drug Des Dev Ther. 2013;7:1179–86.CrossRef Zhuang HQ, Yuan ZY, Wang J, Zhao LJ, Pang QS, Wang P. Phase II study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma. Drug Des Dev Ther. 2013;7:1179–86.CrossRef
11.
go back to reference Janjigian YY, Park BJ, Zakowski MF, Ladanyi M, Pao W, D'Angelo SP, et al. Impact on disease-free survival of adjuvant Erlotinib or Gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations. J Thorac Oncol. 2011;6(3):569–75.CrossRef Janjigian YY, Park BJ, Zakowski MF, Ladanyi M, Pao W, D'Angelo SP, et al. Impact on disease-free survival of adjuvant Erlotinib or Gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations. J Thorac Oncol. 2011;6(3):569–75.CrossRef
12.
go back to reference Yang CJ, Hung JY, Tsai MJ, Wu KL, Liu TC, Chou SH, et al. The salvage therapy in lung adenocarcinoma initially harbored susceptible EGFR mutation and acquired resistance occurred to the first-line gefitinib and second-line cytotoxic chemotherapy. BMC Pharmacol Toxicol. 2017;18. Yang CJ, Hung JY, Tsai MJ, Wu KL, Liu TC, Chou SH, et al. The salvage therapy in lung adenocarcinoma initially harbored susceptible EGFR mutation and acquired resistance occurred to the first-line gefitinib and second-line cytotoxic chemotherapy. BMC Pharmacol Toxicol. 2017;18.
13.
go back to reference Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Mol Cancer Ther. 2007;6(12):3333S–4S. Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Mol Cancer Ther. 2007;6(12):3333S–4S.
14.
go back to reference Asami K, Kawahara M, Atagi S, Kawaguchi T, Okishio K. Duration of prior gefitinib treatment predicts survival potential in patients with lung adenocarcinoma receiving subsequent erlotinib. Lung Cancer. 2011;73(2):211–6.CrossRef Asami K, Kawahara M, Atagi S, Kawaguchi T, Okishio K. Duration of prior gefitinib treatment predicts survival potential in patients with lung adenocarcinoma receiving subsequent erlotinib. Lung Cancer. 2011;73(2):211–6.CrossRef
15.
go back to reference Cardona AF, Arrieta O, Zapata MI, Rojas L, Wills B, Reguart N, et al. Acquired resistance to Erlotinib in EGFR mutation-positive lung adenocarcinoma among Hispanics (CLICaP). Target Oncol. 2017;12(4):513–23.CrossRef Cardona AF, Arrieta O, Zapata MI, Rojas L, Wills B, Reguart N, et al. Acquired resistance to Erlotinib in EGFR mutation-positive lung adenocarcinoma among Hispanics (CLICaP). Target Oncol. 2017;12(4):513–23.CrossRef
16.
go back to reference Pan QL, Pao W, Ladanyi M. Rapid polymerase chain reaction-based detection of epidermal growth factor receptor gene mutations in lung adenocarcinomas. J Mol Diagn. 2005;7(3):396–403.CrossRef Pan QL, Pao W, Ladanyi M. Rapid polymerase chain reaction-based detection of epidermal growth factor receptor gene mutations in lung adenocarcinomas. J Mol Diagn. 2005;7(3):396–403.CrossRef
17.
go back to reference Pao W, Wang TY, Riely GJ, Miller VA, Pan QL, Ladanyi M, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2005;2(1):57–61.CrossRef Pao W, Wang TY, Riely GJ, Miller VA, Pan QL, Ladanyi M, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2005;2(1):57–61.CrossRef
18.
go back to reference Sholf LM, Janne PA, Jackman DM, Joshi VA. Lindeman NI. EGFR kinase domain mutations, but not copy number, predict response to erlotinib and gefitinib in patients with advanced lung adenocarcinoma. J Mol Diagn. 2007;9(5):692. Sholf LM, Janne PA, Jackman DM, Joshi VA. Lindeman NI. EGFR kinase domain mutations, but not copy number, predict response to erlotinib and gefitinib in patients with advanced lung adenocarcinoma. J Mol Diagn. 2007;9(5):692.
19.
go back to reference Tanaka K, Hida T, Oya Y, Oguri T, Yoshida T, Shimizu J, et al. EGFR mutation impact on definitive concurrent Chemoradiation therapy for inoperable stage III adenocarcinoma. J Thorac Oncol. 2015;10(12):1720–5.CrossRef Tanaka K, Hida T, Oya Y, Oguri T, Yoshida T, Shimizu J, et al. EGFR mutation impact on definitive concurrent Chemoradiation therapy for inoperable stage III adenocarcinoma. J Thorac Oncol. 2015;10(12):1720–5.CrossRef
20.
go back to reference Yang JJ, Zhou Q, Yan HH, Zhang XC, Chen HJ, Tu HY, et al. A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. Br J Cancer. 2017;116(5):568–74.CrossRef Yang JJ, Zhou Q, Yan HH, Zhang XC, Chen HJ, Tu HY, et al. A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. Br J Cancer. 2017;116(5):568–74.CrossRef
21.
go back to reference Tetsumoto S, Osa A, Kijima T, Minami T, Hirata H, Takahashi R, et al. Two cases of leptomeningeal metastases from lung adenocarcinoma which progressed during gefitinib therapy but responded to erlotinib. Int J Clin Oncol. 2012;17(2):155–9.CrossRef Tetsumoto S, Osa A, Kijima T, Minami T, Hirata H, Takahashi R, et al. Two cases of leptomeningeal metastases from lung adenocarcinoma which progressed during gefitinib therapy but responded to erlotinib. Int J Clin Oncol. 2012;17(2):155–9.CrossRef
22.
go back to reference Xu Y, Liu HY, Chen J, Zhou QH. Acquired resistance of lung adenocarcinoma to EGFR-tyrosine kinase inhibitors gefitinib and erlotinib. Cancer Biol Ther. 2010;9(8):572–82.CrossRef Xu Y, Liu HY, Chen J, Zhou QH. Acquired resistance of lung adenocarcinoma to EGFR-tyrosine kinase inhibitors gefitinib and erlotinib. Cancer Biol Ther. 2010;9(8):572–82.CrossRef
23.
go back to reference Normando SRC, Cruz FM, del Giglio A. Cumulative meta-analysis of epidermal growth factor receptor-tyrosine kinase inhibitors as first-line therapy in metastatic non-small-cell lung cancer. Anti-Cancer Drugs. 2015;26(9):995–1003.CrossRef Normando SRC, Cruz FM, del Giglio A. Cumulative meta-analysis of epidermal growth factor receptor-tyrosine kinase inhibitors as first-line therapy in metastatic non-small-cell lung cancer. Anti-Cancer Drugs. 2015;26(9):995–1003.CrossRef
24.
go back to reference Shen YC, Tseng GC, Tu CY, Chen WC, Liao WC, Chen WC, et al. Comparing the effects of afatinib with gefitinib or Erlotinib in patients with advanced-stage lung adenocarcinoma harboring non-classical epidermal growth factor receptor mutations. Lung Cancer. 2017;110:56–62.CrossRef Shen YC, Tseng GC, Tu CY, Chen WC, Liao WC, Chen WC, et al. Comparing the effects of afatinib with gefitinib or Erlotinib in patients with advanced-stage lung adenocarcinoma harboring non-classical epidermal growth factor receptor mutations. Lung Cancer. 2017;110:56–62.CrossRef
25.
go back to reference Katayama T, Shimizu J, Suda K, Onozato R, Fukui T, Ito S, et al. Efficacy of Erlotinib for brain and leptomeningeal metastases in patients with lung adenocarcinoma who showed initial good response to Gefitinib. J Thorac Oncol. 2009;4(11):1415–9.CrossRef Katayama T, Shimizu J, Suda K, Onozato R, Fukui T, Ito S, et al. Efficacy of Erlotinib for brain and leptomeningeal metastases in patients with lung adenocarcinoma who showed initial good response to Gefitinib. J Thorac Oncol. 2009;4(11):1415–9.CrossRef
26.
go back to reference Wu SG, Shih JY, Yu CJ, Yang PC. Lung adenocarcinoma with good response to erlotinib after gefitinib treatment failure and acquired T790M mutation. J Thorac Oncol. 2008;3(4):451–2.CrossRef Wu SG, Shih JY, Yu CJ, Yang PC. Lung adenocarcinoma with good response to erlotinib after gefitinib treatment failure and acquired T790M mutation. J Thorac Oncol. 2008;3(4):451–2.CrossRef
27.
go back to reference Yu SF, Wang Y, Li JL, Hao XZ, Wang B, Wang ZP, et al. Gefitinib versus erlotinib as salvage treatment for lung adenocarcinoma patients who benefited from the initial gefitinib: a retrospective study. Thorac Cancer. 2013;4(2):109–16.CrossRef Yu SF, Wang Y, Li JL, Hao XZ, Wang B, Wang ZP, et al. Gefitinib versus erlotinib as salvage treatment for lung adenocarcinoma patients who benefited from the initial gefitinib: a retrospective study. Thorac Cancer. 2013;4(2):109–16.CrossRef
28.
go back to reference Xing PY, Li JL, Shi YK, Zhang XR. Recurrent response to advanced lung adenocarcinoma with erlotinib developing leptomeningeal metastases during gefitinib therapy and two case reports. Thorac Cancer. 2014;5(1):38–42.CrossRef Xing PY, Li JL, Shi YK, Zhang XR. Recurrent response to advanced lung adenocarcinoma with erlotinib developing leptomeningeal metastases during gefitinib therapy and two case reports. Thorac Cancer. 2014;5(1):38–42.CrossRef
29.
go back to reference Chang CH, Lee CH, Wang JY. Gefitinib or Erlotinib for previously treated lung adenocarcinoma: which is superior? J Clin Oncol. 2017;35(12):1374.CrossRef Chang CH, Lee CH, Wang JY. Gefitinib or Erlotinib for previously treated lung adenocarcinoma: which is superior? J Clin Oncol. 2017;35(12):1374.CrossRef
30.
go back to reference Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46.CrossRef Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46.CrossRef
31.
go back to reference Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015;26(9):1877–83.CrossRef Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015;26(9):1877–83.CrossRef
32.
go back to reference Fukui T, Otani S, Hataishi R, Jiang SX, Nishii Y, Igawa S, et al. Successful rechallenge with erlotinib in a patient with EGFR-mutant lung adenocarcinoma who developed gefitinib-related interstitial lung disease. Cancer Chemother Pharmacol. 2010;65(4):803–6.CrossRef Fukui T, Otani S, Hataishi R, Jiang SX, Nishii Y, Igawa S, et al. Successful rechallenge with erlotinib in a patient with EGFR-mutant lung adenocarcinoma who developed gefitinib-related interstitial lung disease. Cancer Chemother Pharmacol. 2010;65(4):803–6.CrossRef
Metadata
Title
Erlotinib versus gefitinib for brain metastases in Asian patients with exon 19 EGFR-mutant lung adenocarcinoma: a retrospective, multicenter study
Authors
Ye Jiang
Jing Zhang
Juanjuan Huang
Bo Xu
Ning Li
Lei Cao
Mingdong Zhao
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2018
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-018-0734-1

Other articles of this Issue 1/2018

BMC Pulmonary Medicine 1/2018 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.