바로가기메뉴

본문 바로가기 주메뉴 바로가기

Tuberculosis & Respiratory Diseases

Article Contents

Prev Next
e-Submission

Vol.80 No.2
Citation Share

Predictive Factors for Switched EGFR-TKI Retreatment in Patients with EGFR-Mutant Non-Small Cell Lung Cancer

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2017, v.80 no.2, pp.187-193







& (2017). Predictive Factors for Switched EGFR-TKI Retreatment in Patients with EGFR-Mutant Non-Small Cell Lung Cancer. Tuberculosis & Respiratory Diseases, 80(2), 187-193.
  • Downloaded
  • Viewed
PDF Download

Abstract

Background: Third-generation tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKIs) have proved efficacious in treating non-small cell lung cancer (NSCLC) patients with acquired resistance resulting from the T790M mutation. However, since almost 50% patients with the acquired resistance do not harbor the T790M mutation, retreatment with first- or second-generation EGFR-TKIs may be a more viable therapeutic option. Here, we identified positive response predictors to retreatment, in patients who switched to a different EGFR-TKI, following initial treatment failure. Methods: This study retrospectively reviewed the medical records of 42 NSCLC patients with EGFR mutations, whose cancers had progressed following initial treatment with gefitinib or erlotinib, and who had switched to a different firstgeneration EGFR-TKI during subsequent retreatment. To identify high response rate predictors in the changed EGFR-TKI retreatment, we analyzed the relationship between clinical and demographic parameters, and positive clinical outcomes, following retreatment with EGFR-TKI. Results: Overall, 30 (71.4%) patients received gefitinib and 12 (28.6%) patients received erlotinib as their first EGFR-TKI treatment. Following retreatment with a different EGFR-TKI, the overall response and disease control rates were 21.4% and 64.3%, respectively. There was no significant association between their overall responses. The median progressionfree survival (PFS) after retreatment was 2.0 months. However, PFS was significantly longer in patients whose time to progression was ≥10 months following initial EGFR-TKI treatment, who had a mutation of exon 19, or whose treatment interval was <90 days. Conclusion: In patients with acquired resistance to initial EGFR-TKI therapy, switched EGFR-TKI retreatment may be a salvage therapy for individuals possessing positive retreatment response predictors.

keywords
Carcinoma, Non-Small-Cell Lung, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Retreatment, Predictive

Reference

1.

1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide:sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86.

2.

2. Charloux A, Quoix E, Wolkove N, Small D, Pauli G, Kreisman H. The increasing incidence of lung adenocarcinoma: reality or artefact? A review of the epidemiology of lung adenocarcinoma. Int J Epidemiol 1997;26:14-23.

3.

3. Park JY, Jang SH. Epidemiology of lung vancer in Korea: recent trends. Tuberc Respir Dis 2016;79:58-69.

4.

4. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92-8.

5.

5. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947-57.

6.

6. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, et al. Gefitinib or chemotherapy for non-smallcell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380-8.

7.

7. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011;12:735-42.

8.

8. Su KY, Chen HY, Li KC, Kuo ML, Yang JC, Chan WK, et al. Pretreatment epidermal growth factor receptor (EGFR ) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non-small-cell lung cancer. J Clin Oncol 2012;30:433-40.

9.

9. Vikis H, Sato M, James M, Wang D, Wang Y, Wang M, et al. EGFR -T790M is a rare lung cancer susceptibility allele with enhanced kinase activity. Cancer Res 2007;67:4665-70.

10.

10. Kuang Y, Rogers A, Yeap BY, Wang L, Makrigiorgos M, Vetrand K, et al. Noninvasive detection of EGFR T790M in gefitinib or erlotinib resistant non-small cell lung cancer. Clin Cancer Res 2009;15:2630-6.

11.

11. Yu HA, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W, et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR -mutant lung cancers. Clin Cancer Res 2013;19:2240-7.

12.

12. Gainor JF, Shaw AT. Emerging paradigms in the development of resistance to tyrosine kinase inhibitors in lung cancer. J Clin Oncol 2013;31:3987-96.

13.

13. Zhang Z, Lee JC, Lin L, Olivas V, Au V, LaFramboise T, et al. Activation of the AXL kinase causes resistance to EGFRtargeted therapy in lung cancer. Nat Genet 2012;44:852-60.

14.

14. Lee JC, Jang SH, Lee KY, Kim YC. Treatment of non-small cell lung carcinoma after failure of epidermal growth factor receptor tyrosine kinase inhibitor. Cancer Res Treat 2013;45:79-85.

15.

15. Nurwidya F, Takahashi F, Murakami A, Takahashi K. Epithelial mesenchymal transition in drug resistance and metastasis of lung cancer. Cancer Res Treat 2012;44:151-6.

16.

16. Lee DH, Kim SW, Suh C, Yoon DH, Yi EJ, Lee JS. Phase II study of erlotinib as a salvage treatment for non-small-cell lung cancer patients after failure of gefitinib treatment. Ann Oncol 2008;19:2039-42.

17.

17. Wong AS, Soong R, Seah SB, Lim SW, Chuah KL, Nga ME, et al. Evidence for disease control with erlotinib after gefitinib failure in typical gefitinib-sensitive Asian patients with nonsmall cell lung cancer. J Thorac Oncol 2008;3:400-4.

18.

18. Cho BC, Im CK, Park MS, Kim SK, Chang J, Park JP, et al. Phase II study of erlotinib in advanced non-small-cell lung cancer after failure of gefitinib. J Clin Oncol 2007;25:2528-33.

19.

19. Becker A, Crombag L, Heideman DA, Thunnissen FB, van Wijk AW, Postmus PE, 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;47:2603-6.

20.

20. Song Z, Yu X, He C, Zhang B, Zhang Y. Re-administration after the failure of gefitinib or erlotinib in patients with advanced non-small cell lung cancer. J Thorac Dis 2013;5:400-5.

21.

21. Oh IJ, Ban HJ, Kim KS, Kim YC. Retreatment of gefitinib in patients with non-small-cell lung cancer who previously controlled to gefitinib: a single-arm, open-label, phase II study. Lung Cancer 2012;77:121-7.

22.

22. Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 2011;3:75ra26.

23.

23. Arcila ME, Oxnard GR, Nafa K, Riely GJ, Solomon SB, Zakowski MF, et al. Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay. Clin Cancer Res 2011;17:1169-80.

24.

24. Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, et al. EGFR mutation and resistance of nonsmall-cell lung cancer to gefitinib. N Engl J Med 2005;352:786-92.

25.

25. Yokouchi H, Yamazaki K, Kinoshita I, Konishi J, Asahina H, Sukoh N, et al. Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer. BMC Cancer 2007;7:51.

26.

26. Costa DB, Nguyen KS, Cho BC, Sequist LV, Jackman DM, Riely GJ, et al. Effects of erlotinib in EGFR mutated non-small cell lung cancers with resistance to gefitinib. Clin Cancer Res 2008;14:7060-7.

27.

27. 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;3:912-4.

28.

28. Hata A, Katakami N, Yoshioka H, Fujita S, Kunimasa K, Nanjo S, et al. Erlotinib after gefitinib failure in relapsed non-small cell lung cancer: clinical benefit with optimal patient selection. Lung Cancer 2011;74:268-73.

29.

29. Li J, Hao X, Wang Y, Zhang X, Shi Y. Clinical response to gefitinib retreatment of lung adenocarcinoma patients who benefited from an initial gefitinib therapy: a retrospective analysis. Zhongguo Fei Ai Za Zhi 2012;15:44-8.

30.

30. Tomizawa Y, Fujita Y, Tamura A, Shirai M, Shibata S, Kawabata T, et al. Effect of gefitinib re-challenge to initial gefitinib responder with non-small cell lung cancer followed by chemotherapy. Lung Cancer 2010;68:269-72.

31.

31. Zwitter M, Rajer M, Stanic K, Vrankar M, Doma A, Cuderman A, et al. Intercalated chemotherapy and erlotinib for nonsmall cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR ) mutations. Cancer Biol Ther 2016;17:833-9.

32.

32. Tang C, Li X, Guo W, Li J, Qin H, Wang W, et al. How to make the choice in the retreatment of EGFR-TKI for advanced NSCLC patients who benefited from prior gefitinib therapy:the original drug or switching to a second EGFR-TKI? Zhongguo Fei Ai Za Zhi 2013;16:345-52.

33.

33. An T, Huang Z, Wang Y, Wang Z, Bai H, Wang J. Retreatment with epidermal growth factor receptor inhibitor after initial failure in advanced non-small cell lung cancer. Zhongguo Fei Ai Za Zhi 2011;14:261-5.

34.

34. Xia GH, Zeng Y, Fang Y, Yu SR, Wang L, Shi MQ, et al. Effect of EGFR-TKI retreatment following chemotherapy for advanced non-small cell lung cancer patients who underwent EGFRTKI. Cancer Biol Med 2014;11:270-6.

35.

35. Chin TM, Quinlan MP, Singh A, Sequist LV, Lynch TJ, Haber DA, et al. Reduced Erlotinib sensitivity of epidermal growth factor receptor-mutant non-small cell lung cancer following cisplatin exposure: a cell culture model of second-line erlotinib treatment. Clin Cancer Res 2008;14:6867-76.

36.

36. Ettinger DS, Wood DE, Akerley W, Bazhenova LA, Borghaei H, Camidge DR, et al. NCCN guidelines insights: non-small cell lung cancer, version 4.2016. J Natl Compr Canc Netw 2016;14:255-64.

Tuberculosis & Respiratory Diseases

e-Submission OA Policy