Journal of Cancer Research and Clinical Oncology

, Volume 140, Issue 3, pp 427–433

Different treatment orders achieved similar clinical results: a retrospective study for retreatment of epidermal growth factor receptor tyrosine kinase inhibitors in 120 patients with non-small-cell lung cancer

  • Chuanhao Tang
  • Hongjun Gao
  • Xiaoyan Li
  • Yi Liu
  • Jianjie Li
  • Haifeng Qin
  • Weixia Wang
  • Lili Qu
  • Juan An
  • Shaoxing Yang
  • Xiaoqing Liu
Original Paper

Abstract

Background

It was reported the retreatment of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) may bring benefit to non-small-cell lung cancer (NSCLC) patients who benefited previously. Nevertheless, the treatment order in most of the prior literature was gefitinib (G) to erlotinib (E), and little was known about whether other treatment order may also bring benefit to the patients.

Methods

One hundred and twenty NSCLC patients who received EGFR-TKIs treatment twice were enrolled in this study. The safety and effectiveness of the second EGFR-TKIs administration, as well as the influencing factors that contribute to this process, were analyzed retrospectively.

Results

Forty-nine (40.8 %) patients were retreated with same kind of EGFR-TKIs: 30 (25 %) were G and 19 (15.8 %) were E. Seventy-one (59.2 %) patients switched to another kind: 55 (45.8 %) were G to E and 16 (13.4 %) were the reverse. Notably, no differences in clinical benefits were found among the four different treatment orders. For the second administration, the adverse effects of all patients were generally classified as grade I–II and the 1-year survival rate reached 32.5 %. The objective response rate, disease control rate, median progression-free survival (PFS), and overall survival was 10.0 % (12/120), 52.5 % (63/120), 2.3 (95 % CI 1.5–3.0) months and 8.0 (95 % CI 7.0–8.5) months, respectively. The univariate and multivariate analyses revealed that those patients who benefited from prior EGFR-TKIs were easier to get benefit from the second administration, and the strongest beneficial indicators of the retreatment were PFS of the initial EGFR-TKIs (≥6 months, HR 0.611, 95 % CI 0.354–0.901, P = 0.0076) and time interval between the two EGFR-TKIs treatment (≥4 months, HR 0.529, 95 % CI 0.328–0.852, P = 0.0088).

Conclusion

Those patients who benefited from prior EGFR-TKIs were easier to get benefit from the second administration. A time interval of ≥4 months may improve the retreatment, but differences in clinical benefit were not found among different treatment orders. If the retrospective result could be validated further in the future, it would be helpful for rational administration of EGFR-TKIs.

Keywords

Non-small-cell lung cancer Epidermal growth factor receptor tyrosine kinase inhibitor Gefitinib Erlotinib 

References

  1. Ahn MJ, Lee J, Park YH, Ahn JS, Ziogas A, Zell JA et al (2010) Korean ethnicity as compared with white ethnicity is an independent favorable prognostic factor for overall survival in non-small cell lung cancer before and after the oral epidermal growth factor receptor tyrosine kinase inhibitor era. J Thorac Oncol 5(8):1185–1196PubMedGoogle Scholar
  2. Becker A, Crombag L, Heideman DA, Thunnissen FB, van Wijk AW, Postmus PE et al (2011) 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 47(17):2603–2606PubMedGoogle Scholar
  3. Cho BC, Im CK, Park MS, Kim SK, Chang J, Park JP et al (2007) Phase II study of erlotinib in advanced non-small-cell lung cancer after failure of gefitinib. J Clin Oncol 25:2528–2533PubMedGoogle Scholar
  4. Costa DB, Nguyen KS, Cho BC, Sequist LV, Jackman DM, Riely GJ et al (2008) Effects of erlotinib in EGFR mutated non-small cell lung cancers with resistance to gefitinib. Clin Cancer Res 14:7060–7067PubMedCentralPubMedGoogle Scholar
  5. Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A (2013) Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol 10(8):472–484PubMedGoogle Scholar
  6. Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF et al (2013) Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 368(13):1199–1209PubMedGoogle Scholar
  7. Hata A, Katakami N, Yoshioka H, Fujita S, Kunimasa K, Nanjo S et al (2011) Erlotinib after gefitinib failure in relapsed non-small cell lung cancer: clinical benefit with optimal patient selection. Lung Cancer 74(2):268–273PubMedGoogle Scholar
  8. Kaira K, Naito T, Takahashi T, Ayabe E, Shimoyama R, Kaira R et al (2010) Pooled analysis of the reports of erlotinib after failure of gefitinib for non-small cell lung cancer. Lung Cancer 68(1):99–104PubMedGoogle Scholar
  9. Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M et al (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352(8):786–792PubMedGoogle Scholar
  10. Lee DH, Kim SW, Suh C, Yoon DH, Yi EJ, Lee JS (2008) Phase II study of erlotinib as a salvage treatment for non-small-cell lung cancer patients after failure of gefitinib treatment. Ann Oncol 19(12):2039–2042PubMedGoogle Scholar
  11. Liu Y, Liu B, Li XY, Li JJ, Qin HF, Tang CH et al (2011) A comparison of ARMS and direct sequencing for EGFR mutation analysis and tyrosine kinase inhibitors treatment prediction in body fluid samples of non-small-cell lung cancer patients. J Exp Clin Cancer Res 30:111PubMedGoogle Scholar
  12. 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 350(21):2129–2139PubMedGoogle Scholar
  13. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H et al (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388PubMedGoogle Scholar
  14. Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV et al (2008) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359(4):366–377PubMedCentralPubMedGoogle Scholar
  15. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J et al (2010) 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 11:121–128PubMedGoogle Scholar
  16. 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 361:947–957PubMedGoogle Scholar
  17. Ni X, Zhuo M, Su Z, Duan J, Gao Y, Wang Z et al (2013) Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients. Proc Natl Acad Sci USA 110(52):21083–21088PubMedGoogle Scholar
  18. Oh IJ, Ban HJ, Kim KS, Kim YC (2012) 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 77(1):121–127PubMedGoogle Scholar
  19. Oxnard GR, Arcila ME, Chmielecki J, Ladanyi M, Miller VA, Pao W (2011) New strategies in overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer. Clin Cancer Res 17(17):5530–5537PubMedCentralPubMedGoogle Scholar
  20. Paez JG, Jänne 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 304(5676):1497–1500PubMedGoogle Scholar
  21. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I et al (2004) EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 101(36):13306–13311PubMedGoogle Scholar
  22. 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 361(10):958–967PubMedGoogle Scholar
  23. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E et al (2012) 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 13(3):239–246PubMedGoogle Scholar
  24. Sequist LV, Bell DW, Lynch TJ, Haber DA (2007) Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J Clin Oncol 25(5):587–595PubMedGoogle Scholar
  25. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63(1):11–30PubMedGoogle Scholar
  26. Takano T, Fukui T, Ohe Y, Tsuta K, Yamamoto S, Nokihara H et al (2008) EGFR mutations predict survival benefit from gefitinib in patients with advanced lung adenocarcinoma: a historical comparison of patients treated before and after gefitinib approval in Japan. J Clin Oncol 26(34):5589–5595PubMedGoogle Scholar
  27. Watanabe S, Tanaka J, Ota T, Kondo R, Tanaka H, Kagamu H et al (2011) Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis. BMC Cancer 11:1PubMedCentralPubMedGoogle Scholar
  28. Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G et al (2013) Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol 14(8):777–786PubMedGoogle Scholar
  29. Zhang L, Ma S, Song X, Han B, Cheng Y, Huang C et al (2012) Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804): a multicentre, double-blind randomised phase 3 trial. Lancet Oncol 13(5):466–475PubMedGoogle Scholar
  30. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C et al (2011) 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 12(8):735–742PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Chuanhao Tang
    • 1
  • Hongjun Gao
    • 1
  • Xiaoyan Li
    • 1
  • Yi Liu
    • 2
  • Jianjie Li
    • 1
  • Haifeng Qin
    • 1
  • Weixia Wang
    • 1
  • Lili Qu
    • 1
  • Juan An
    • 1
  • Shaoxing Yang
    • 1
  • Xiaoqing Liu
    • 1
  1. 1.Department of Lung CancerAffiliated Hospital of Academy of Military Medical SciencesBeijingChina
  2. 2.Laboratory of Oncology, Translational Medicine CenterAffiliated Hospital of Academy of Military Medical SciencesBeijingChina

Personalised recommendations