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Journal of Cancer Research and Clinical Oncology

, Volume 142, Issue 6, pp 1325–1330 | Cite as

Efficacy of EGFR tyrosine kinase inhibitors for non-adenocarcinoma lung cancer patients harboring EGFR-sensitizing mutations in China

  • Jianlin Xu
  • Yanwei Zhang
  • Bo Jin
  • Tianqing Chu
  • Xue Dong
  • Haitang Yang
  • Dan Wu
  • Yuqing Lou
  • Xueyan Zhang
  • Huiming Wang
  • Baohui HanEmail author
Original Article – Clinical Oncology

Abstract

Purpose

EGFR tyrosine kinase inhibitors (TKIs) have been established as standard therapy for EGFR-mutated adenocarcinomas; for non-adenocarcinoma non-small cell lung cancer (NSCLC) patients, this therapy remains debatable.

Methods

Stage IIIB/IV patients with non-adenocarcinoma NSCLC who underwent EGFR testing were identified at the Shanghai Chest Hospital from January 2009 to September 2014.

Results

A total of 51 patients with EGFR-sensitizing mutations [26 patients with squamous cell carcinoma (SCC), 15 patients with adenosquamous cell carcinoma (ASC), and 10 patients with large cell lung carcinoma (LCLC)] were available for analysis of EGFR TKI treatment efficacy. The progression-free survival (PFS) for the 51 patients harboring EGFR-sensitizing mutations was 4.93 months (95 % CI 3.93–5.93). The PFS for the SCC, ASC, and LCLC patients was 3.98 months (95 % CI 3.32–4.63), 8.08 months (95 % CI 4.17–12.00), and 4.40 months (95 % CI 1.56–7.24), respectively. Among the 51 non-adenocarcinoma NSCLC patients, the PFS of the non-smokers and smokers was 5.49 months (95 % CI 3.28–7.70) and 3.78 months (95 % CI 2.61–4.95), respectively (P = 0.036). The PFS for the patients with a deletion in exon 19 and for those with an exon 21 L858R mutation was 5.16 months (95 % CI 4.21–6.11) and 4.04 months (95 % CI 2.35–5.73), respectively (P = 0.414).

Conclusions

EGFR TKIs could be an option for the treatment of EGFR-mutated non-adenocarcinoma NSCLC, especially for patients with adenosquamous histology and non-smokers.

Keywords

Non-adenocarcinoma NSCLC EGFR Tyrosine kinase inhibitors 

Notes

Acknowledgments

The authors would like to acknowledge support from the Department of Pathology of Shanghai Chest Hospital. We also thank Hua Zhong, Chunlei Shi, Aiqing Gu, Liwen Xiong, and Yizhuo Zhao for their provision of study materials or patients for this study.

Funding

This work was supported by Key Projects of the Biomedicine Department, Science and Technology Commission of Shanghai Municipality (Project No. 11411951200). The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors have stated that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. Chou TY, Chiu CH, Li LH et al (2005) Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer. Clin Cancer Res 11:3750–3757CrossRefPubMedGoogle Scholar
  2. Detterbeck FC, Boffa DJ, Tanoue LT (2009) The new lung cancer staging system. Chest 136:260–271CrossRefPubMedGoogle Scholar
  3. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefPubMedGoogle Scholar
  4. Fang W, Zhang J, Liang W et al (2013) Efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors for Chinese patients with squamous cell carcinoma of lung harboring EGFR mutation. J Thorac Dis 5:585–592PubMedPubMedCentralGoogle Scholar
  5. Govindan R, Ding L, Griffith M et al (2012) Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 150:1121–1134CrossRefPubMedPubMedCentralGoogle Scholar
  6. Han B, Tjulandin S, Hagiwara K et al (2015) Determining the prevalence of EGFR mutations in Asian and Russian patients with advanced non-small-cell lung cancer (ANSCLC) of adenocarcinoma (ADC) and non-ADC histology: ignite study. Ann Oncol 26(suppl 1):i29–i30CrossRefGoogle Scholar
  7. Hata A, Katakami N, Yoshioka H et al (2013) How sensitive are epidermal growth factor receptor-tyrosine kinase inhibitors for squamous cell carcinoma of the lung harboring EGFR gene-sensitive mutations? J Thorac Oncol 8:89–95CrossRefPubMedGoogle Scholar
  8. Hecht SS (2012) Lung carcinogenesis by tobacco smoke. Int J Cancer 131:2724–2732CrossRefPubMedPubMedCentralGoogle Scholar
  9. Kang SM, Kang HJ, Shin JH et al (2007) Identical epidermal growth factor receptor mutations in adenocarcinomatous and squamous cell carcinomatous components of adenosquamous carcinoma of the lung. Cancer 109:581–587CrossRefPubMedGoogle Scholar
  10. Kim MH, Kim HR, Cho BC et al (2014) Impact of cigarette smoking on response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in lung adenocarcinoma with activating EGFR mutations. Lung Cancer 84:196–202CrossRefPubMedGoogle Scholar
  11. Leighl NB, Rekhtman N, Biermann WA et al (2014) Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists/International Association for the study of lung cancer/association for molecular pathology guideline. J Clin Oncol 32:3673–3679CrossRefPubMedGoogle Scholar
  12. Lynch TJ, Bell DW, Sordella R 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 350:2129–2139CrossRefPubMedGoogle Scholar
  13. Maemondo M, Inoue A, Kobayashi K et al (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388CrossRefPubMedGoogle Scholar
  14. Mok TS, Wu YL, Thongprasert S et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947–957CrossRefPubMedGoogle Scholar
  15. Ohtsuka K, Ohnishi H, Fujiwara M et al (2007) Abnormalities of epidermal growth factor receptor in lung squamous-cell carcinomas, adenosquamous carcinomas, and large-cell carcinomas: tyrosine kinase domain mutations are not rare in tumors with an adenocarcinoma component. Cancer 109:741–750CrossRefPubMedGoogle Scholar
  16. Petersen I, Warth A (2015) Lung cancer: developments, concepts, and specific aspects of the new WHO classification. J Cancer Res Clin Oncol. doi: 10.1007/s00432-015-2004-4 Google Scholar
  17. Rosell R, Moran T, Queralt C et al (2009) Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 361:958–967CrossRefPubMedGoogle Scholar
  18. Shukuya T, Takahashi T, Kaira R et al (2011) Efficacy of gefitinib for non-adenocarcinoma non-small-cell lung cancer patients harboring epidermal growth factor receptor mutations: a pooled analysis of published reports. Cancer Sci 102:1032–1037CrossRefPubMedGoogle Scholar
  19. Sun JM, Won YW, Kim ST et al (2011) The different efficacy of gefitinib or erlotinib according to epidermal growth factor receptor exon 19 and exon 21 mutations in Korean non-small cell lung cancer patients. J Cancer Res Clin Oncol 137:687–694CrossRefPubMedGoogle Scholar
  20. Thatcher N, Chang A, Parikh P et al (2005) Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 366:1527–1537CrossRefPubMedGoogle Scholar
  21. Travis WD, Brambilla E, Muller-Hermelink HK et al (2004) World health organization classification of tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. IARC Press, LyonGoogle Scholar
  22. Wang H, Huang J, Yu X et al (2014) Different efficacy of EGFR tyrosine kinase inhibitors and prognosis in patients with subtypes of EGFR-mutated advanced non-small cell lung cancer: a meta-analysis. J Cancer Res Clin Oncol 140:1901–1909CrossRefPubMedPubMedCentralGoogle Scholar
  23. Wang R, Zhang Y, Pan Y et al (2015) Comprehensive investigation of oncogenic driver mutations in Chinese non-small cell lung cancer patients. Oncotarget 6:34300–34308PubMedPubMedCentralGoogle Scholar
  24. Yang JC, Wu YL, Schuler M et al (2015) Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 16:141–151CrossRefPubMedGoogle Scholar
  25. Zhang L, Ma S, Song X 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 13:466–475CrossRefPubMedGoogle Scholar
  26. Zhang Q, Zhu L, Zhang J (2015a) Epidermal growth factor receptor gene mutation status in pure squamous-cell lung cancer in Chinese patients. BMC Cancer 15:88CrossRefPubMedPubMedCentralGoogle Scholar
  27. Zhang XK, Qin T, Zeng YD et al (2015b) Clinical analysis of 50 Eastern Asian patients with primary pulmonary large-cell neuroendocrine carcinoma. Onco Targets Ther 8:1219–1227CrossRefPubMedPubMedCentralGoogle Scholar
  28. Zhang Y, Kang S, Fang W et al (2015c) Impact of smoking status on EGFR-TKI efficacy for advanced non-small-cell lung cancer in EGFR mutants: a meta-analysis. Clin Lung Cancer 16:144–151CrossRefPubMedGoogle Scholar
  29. Zhou C, Wu YL, Chen G 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 12:735–742CrossRefPubMedGoogle Scholar
  30. Zhu JQ, Zhong WZ, Zhang GC et al (2008) Better survival with EGFR exon 19 than exon 21 mutations in gefitinib-treated non-small cell lung cancer patients is due to differential inhibition of downstream signals. Cancer Lett 265:307–317CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Jianlin Xu
    • 1
  • Yanwei Zhang
    • 1
  • Bo Jin
    • 1
  • Tianqing Chu
    • 1
  • Xue Dong
    • 1
  • Haitang Yang
    • 2
  • Dan Wu
    • 3
  • Yuqing Lou
    • 1
  • Xueyan Zhang
    • 1
  • Huiming Wang
    • 1
  • Baohui Han
    • 1
    Email author
  1. 1.Department of Pulmonary, Shanghai Chest HospitalShanghai Jiaotong UniversityShanghaiChina
  2. 2.Department of Thoracic Surgery, Shanghai Chest HospitalShanghai Jiaotong UniversityShanghaiChina
  3. 3.Central Laboratory, Shanghai Chest HospitalShanghai Jiaotong UniversityShanghaiChina

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