The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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Clinical efficacy of erlotinib, a salvage treatment for non-small cell lung cancer patients following gefitinib failure

  • Cho, Kyoung Min (Department of Internal Medicine, Seoul National University Hospital) ;
  • Keam, Bhumsuk (Department of Internal Medicine, Seoul National University Hospital) ;
  • Kim, Tae Min (Department of Internal Medicine, Seoul National University Hospital) ;
  • Lee, Se-Hoon (Department of Internal Medicine, Seoul National University Hospital) ;
  • Kim, Dong-Wan (Department of Internal Medicine, Seoul National University Hospital) ;
  • Heo, Dae Seog (Department of Internal Medicine, Seoul National University Hospital)
  • Received : 2014.08.26
  • Accepted : 2014.12.05
  • Published : 2015.11.01
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Abstract

Background/Aims: The purpose of this study was to identify predictive factors for erlotinib treatment in non-small cell lung cancer (NSCLC) patients following gefitinib failure. Methods: Forty-five patients with NSCLC who were treated with erlotinib following gefitinib failure at Seoul National University Hospital between August 2005 and November 2011 were enrolled. Epidermal growth factor receptor (EGFR) mutation status, pathologic findings and other clinical factors, including response to tyrosine kinase inhibitors (TKIs) and progression-free survival (PFS), were evaluated. Results: Of the 45 patients, 40 patients (88.8%) had adenocarcinoma. The following EGFR mutations were observed: five patients with a deletion of exon 19, six patients with an L858R mutation, three patients with wild-type EGFR, and 31 patients with unknown mutations. The response rate of erlotinib was 4.4%, and stable disease was 42.2%. The median PFS for erlotinib was 2.6 months (95% confidence interval, 1.4 to 3.7). Patients with a PFS ${\geq}4$ months during previous gefitinib treatment had a significantly longer PFS with erlotinib (3.3 months vs. 1.6 months, respectively; p < 0.01) than patients with PFS < 4 months with gefitinib. According to multivariate analyses, PFS ${\geq}4$ months for previous gefitinib treatment was significantly associated with prolonged PFS with erlotinib (p = 0.04). However, the response rate of gefitinib and treatment sequence were not associated with prolonged PFS with erlotinib (p = 0.28 and p = 0.67, respectively). Conclusions: Following rechallenge with the EGFR TKI erlotinib following gefitinib failure, patients who showed prolonged PFS with gefitinib benefit from erlotinib. However, further prospective studies are needed to confirm these findings.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

References

  1. Janne PA, Engelman JA, Johnson BE. Epidermal growth factor receptor mutations in non-small-cell lung cancer: implications for treatment and tumor biology. J Clin Oncol 2005;23:3227-3234. https://doi.org/10.1200/JCO.2005.09.985
  2. Baselga J, Arteaga CL. Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 2005;23:2445-2459. https://doi.org/10.1200/JCO.2005.11.890
  3. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380-2388. https://doi.org/10.1056/NEJMoa0909530
  4. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010;11:121-128. https://doi.org/10.1016/S1470-2045(09)70364-X
  5. Cho BC, Im CK, Park MS, et al. Phase II study of erlotinib in advanced non-small-cell lung cancer after failure of gefitinib. J Clin Oncol 2007;25:2528-2533. https://doi.org/10.1200/JCO.2006.10.4166
  6. Sim SH, Han SW, Oh DY, et al. Erlotinib after Gefitinib failure in female never-smoker Asian patients with pulmonary adenocarcinoma. Lung Cancer 2009;65:204-207. https://doi.org/10.1016/j.lungcan.2008.11.006
  7. Viswanathan A, Pillot G, Govindan R. Lack of response to erlotinib after progression on gefitinib in patients with advanced non-small cell lung cancer. Lung Cancer 2005;50:417-418. https://doi.org/10.1016/j.lungcan.2005.07.004
  8. Kaira K, Naito T, Takahashi T, et al. Pooled analysis of the reports of erlotinib after failure of gefitinib for non-small cell lung cancer. Lung Cancer 2010;68:99-104. https://doi.org/10.1016/j.lungcan.2009.05.006
  9. Li J, Zhao M, He P, Hidalgo M, Baker SD. Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res 2007;13:3731-3737. https://doi.org/10.1158/1078-0432.CCR-07-0088
  10. Comis RL. The current situation: erlotinib (Tarceva) and gefitinib (Iressa) in non-small cell lung cancer. Oncologist 2005;10:467-470. https://doi.org/10.1634/theoncologist.10-7-467
  11. Leveque D. Pharmacokinetics of gefitinib and erlotinib. Lancet Oncol 2011;12:1093.
  12. Lee DH, Kim SW, Suh C, Yoon DH, Yi EJ, Lee JS. Phase II study of erlotinib as a salvage treatment for non-smallcell lung cancer patients after failure of gefitinib treatment. Ann Oncol 2008;19:2039-2042. https://doi.org/10.1093/annonc/mdn423
  13. Wong AS, Soong R, Seah SB, et al. Evidence for disease control with erlotinib after gefitinib failure in typical gefitinib- sensitive Asian patients with non-small cell lung cancer. J Thorac Oncol 2008;3:400-404. https://doi.org/10.1097/JTO.0b013e318168c801
  14. Costa DB, Nguyen KS, Cho BC, et al. Effects of erlotinib in EGFR mutated non-small cell lung cancers with resistance to gefitinib. Clin Cancer Res 2008;14:7060-7067. https://doi.org/10.1158/1078-0432.CCR-08-1455
  15. Grossi F, Rijavec E, Dal Bello MG, et al. The administration of gefitinib in patients with advanced non-small-cell lung cancer after the failure of erlotinib. Cancer Chemother Pharmacol 2012;69:1407-1412. https://doi.org/10.1007/s00280-012-1848-4
  16. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-247. https://doi.org/10.1016/j.ejca.2008.10.026
  17. Kim YT, Kim TY, Lee DS, et al. Molecular changes of epidermal growth factor receptor (EGFR) and KRAS and their impact on the clinical outcomes in surgically resected adenocarcinoma of the lung. Lung Cancer 2008;59:111-118. https://doi.org/10.1016/j.lungcan.2007.08.008
  18. Tomizawa Y, Fujita Y, Tamura A, et al. Effect of gefitinib re-challenge to initial gefitinib responder with non-small cell lung cancer followed by chemotherapy. Lung Cancer 2010;68:269-272. https://doi.org/10.1016/j.lungcan.2009.06.025
  19. Choong NW, Dietrich S, Seiwert TY, et al. Gefitinib response of erlotinib-refractory lung cancer involving meninges: role of EGFR mutation. Nat Clin Pract Oncol 2006;3:50-57. https://doi.org/10.1038/ncponc0400
  20. Zhang Z, Lee JC, Lin L, et al. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet 2012;44:852-860. https://doi.org/10.1038/ng.2330
  21. Kobayashi S, Boggon TJ, Dayaram T, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005;352:786-792. https://doi.org/10.1056/NEJMoa044238
  22. Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005;2:e73. https://doi.org/10.1371/journal.pmed.0020073
  23. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007;316:1039-1043. https://doi.org/10.1126/science.1141478
  24. Yano S, Wang W, Li Q, et al. Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations. Cancer Res 2008;68:9479-9487. https://doi.org/10.1158/0008-5472.CAN-08-1643
  25. Jang SH. Long term therapeutic plan for patients with non-small cell lung cancer harboring EGFR mutation. Tuberc Respir Dis (Seoul) 2014;76:8-14. https://doi.org/10.4046/trd.2014.76.1.8
  26. Becker A, Crombag L, Heideman DA, et al. Retreatment with erlotinib: regain of TKI sensitivity following a drug holiday for patients with NSCLC who initially responded to EGFR-TKI treatment. Eur J Cancer 2011;47:2603-2606. https://doi.org/10.1016/j.ejca.2011.06.046
  27. Guo R, Chen X, Wang T, Zhang Z, Sun J, Shu Y. Subsequent chemotherapy reverses acquired tyrosine kinase inhibitor resistance and restores response to tyrosine kinase inhibitor in advanced non-small-cell lung cancer. BMC Cancer 2011;11:90. https://doi.org/10.1186/1471-2407-11-90
  28. Li XD, Geng YT, Wu CP, et al. Restoration of gefitinib efficacy following chemotherapy in a patient with metastatic non-small cell lung cancer. Onkologie 2010;33:466-469. https://doi.org/10.1159/000319109
  29. Yoshimoto A, Inuzuka K, Kita T, Kawashima A, Kasahara K. Remarkable effect of gefitinib retreatment in a patient with nonsmall cell lung cancer who had a complete response to initial gefitinib. Am J Med Sci 2007;333:221-225. https://doi.org/10.1097/MAJ.0b013e31803b8acb
  30. Hata A, Katakami N, Yoshioka H, et al. Erlotinib after gefitinib failure in relapsed non-small cell lung cancer: clinical benefit with optimal patient selection. Lung Cancer 2011;74:268-273. https://doi.org/10.1016/j.lungcan.2011.03.010
  31. Koyama N, Uchida Y. Clinical significance of erlotinib monotherapy for gefitinib-resistant non-small cell lung cancer with EGFR mutations. Anticancer Res 2013;33:5083-5089.
  32. Vasile E, Tibaldi C, Chella A, Falcone A. Erlotinib after failure of gefitinib in patients with advanced non-small cell lung cancer previously responding to gefitinib. J Thorac Oncol 2008;3:912-914. https://doi.org/10.1097/JTO.0b013e318180275e
  33. Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007;7:169-181. https://doi.org/10.1038/nrc2088

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