Skip to main content
SpringerLink
Log in

Rebiopsy during disease progression in patients treated by TKI for oncogene-addicted NSCLC

  • Original Research
  • Published:
Targeted Oncology Aims and scope Submit manuscript

Abstract

All lung cancer patients with mutant epidermal growth factor receptor (EGFR) or rearranged EML4-ALK eventually develop acquired resistance to treatment. Rebiopsy may give insight into the resistance mechanisms and direct further lines of treatment. Here, we evaluate the potential interest and limitations of rebiopsy. Patients with mutant EGFR or rearranged EML4-ALK non-small cell lung cancer (NSCLC) and acquired resistance to tyrosine kinase inhibitors were included in a retrospective study to determine the percentage of patients who underwent rebiopsy and whether rebiopsy would have been possible, or not, in the remaining patients. In a cohort of 84 patients from 6 institutions, a biopsy had been performed in 39 cases. Biopsy samples were sufficient for histopathological or cytological examination in 35 cases (89.7 %). Complete or partial response had been observed in 84.5 % of patients whose cancer further progressed and who underwent rebiopsy. A biopsy could have been considered in 30 of the 45 remaining patients. Those with brain (N = 9) and bone (N = 2) metastases and/or with contraindications (N = 6) were excluded (two patients had both brain metastases and a contraindication). The rebiopsy target was thoracic in 62 % of cases and on distant metastases in 38 % of cases. Patients with NSCLC and an activating mutation could undergo a rebiopsy in 72 % of cases. A response to treatment does not preclude the possibility of rebiopsy at the time of progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Thun MJ, Hannan LM, Adams-Campbell LL et al (2008) Lung cancer occurrence in never-smokers: an analysis of 13 cohorts and 22 cancer registry studies. PLoS Med 5(9):e185

    Article  PubMed Central  PubMed  Google Scholar 

  2. Schiller JH, Harrington D, Belani CP et al (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346(2):92–98

    Article  CAS  PubMed  Google Scholar 

  3. Soda M, Choi YL, Enomoto M et al (2007) Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448(7153):561–566

    Article  CAS  PubMed  Google Scholar 

  4. Shaw AT, Yeap BY, Solomon BJ et al (2011) Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol 12(11):1004–1012

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Camidge DR, Bang YJ, Kwak EL et al (2012) Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol 13(10):1011–1019

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Kobayashi K, Inoue A, Maemondo M et al (2009) First-line gefitinib versus first-line chemotherapy by carboplatin (CBDCA) plus paclitaxel (TXL) in non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutations: a phase III study (002) by North East Japan Gefitinib Study Group. J Clin Oncol 27(15s (suppl)): abstr 8016

  7. Yang JC-H SM, Yamamoto N, O’Byrne KJ et al (2012) A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. J Clin Oncol 30: abstr LBA7500

  8. 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(25):2380–2388

    Article  CAS  PubMed  Google Scholar 

  9. Arcila ME, Oxnard GR, Nafa K et al (2011) 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 17(5):1169–1180

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Bean J, Riely GJ, Balak M et al (2008) Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma. Clin Cancer Res 14(22):7519–7525

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Sequist L, Waltman B, Dias-Santagata D et al (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 3(75):75ra26

    Article  PubMed Central  PubMed  Google Scholar 

  12. Turke AB, Zejnullahu K, Wu YL, Song Y et al (2010) Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell 17(1):77–88

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Choi YL, Soda M, Yamashita Y et al (2010) EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med 363(18):1734–1739

    Article  CAS  PubMed  Google Scholar 

  14. Doebele RC, Pilling AB, Aisner DL et al (2012) Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res 18(5):1472–1482

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Kim S, Kim TM, Kim DW et al (2013) Heterogeneity of genetic changes associated with acquired crizotinib resistance in ALK-rearranged lung cancer. J Thorac Oncol 8(4):415–422

    Article  CAS  PubMed  Google Scholar 

  16. Overman MJ, Modak J, Kopetz S et al (2013) Use of research biopsies in clinical trials: are risks and benefits adequately discussed? J Clin Oncol 31(1):17–22

    Article  PubMed  Google Scholar 

  17. Peppercorn J (2013) Toward improved understanding of the ethical and clinical issues surrounding mandatory research biopsies. J Clin Oncol 31(1):1–2

    Article  PubMed  Google Scholar 

  18. Bunn PA, Hirsch FR, Doebele RC et al (2010) Biomarkers are here to stay for clinical research and standard care. J Thorac Oncol 5(8):1113–1115

    Article  PubMed  Google Scholar 

  19. Hirsch FR, Wynes MW, Gandara DR et al (2010) The tissue is the issue: personalized medicine for non-small cell lung cancer. Clin Cancer Res 16(20):4909–4911

    Article  CAS  PubMed  Google Scholar 

  20. West H, Oxnard GR, Doebele RC (2013) Acquired resistance to targeted therapies in advanced non-small cell lung cancer: new strategies and new agents. Am Soc Clin Oncol Educ Book. 2013.33.e272

  21. 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(2):228–247

    Article  CAS  PubMed  Google Scholar 

  22. Sequist LV, Waltman BA, Dias-Santagata D et al (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR Inhibitors. Sci Transl Med 3(75):doi:10.1126/scitranslmed.3002003

  23. Yu HA, Arcila ME, Rekhtman N et al (2013) 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 19(8):2240–2247

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Browning ET, Weickhardt AJ, Camidge DR (2013) Response to crizotinib rechallenge after initial progression and intervening chemotherapy in ALK lung cancer. J Thorac Oncol 8(3):E21–E22

    Article  PubMed  Google Scholar 

  25. Doebele RC, Lu X, Sumey C et al (2012) Oncogene status predicts patterns of metastatic spread in treatment-naive non small cell lung cancer. Cancer 118(18):4502–4511

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Yatabe Y, Matsuo K, Mitsudomi T (2011) Heterogeneous distribution of EGFR mutations is extremely rare in lung adenocarcinoma. J Clin Oncol 29(22):2972–2977

    Article  CAS  PubMed  Google Scholar 

  27. VanderLaan PA, Yamaguchi N, Folch E, Boucher DH, Kent MS, Gangadharan SP, Majid A, Goldstein MA, Huberman MS, Kocher ON, Costa DB (2014) Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer. Lung Cancer 84(1):39–44

    Article  PubMed Central  PubMed  Google Scholar 

  28. Singh VM, Salunga RC, Huang VJ, Tran Y, Erlander M, Plumlee P, Peterson MR (2014) Analysis of the effect of various decalcification agents on the quantity and quality of nucleic acid (DNA and RNA) recovered from bone biopsies. Ann Diagn Pathol 17(4):322–326

    Article  Google Scholar 

  29. Isobe K, Hata Y, Kobayashi K et al (2012) Clinical significance of circulating tumor cells and free DNA in non-small cell lung cancer. Anticancer Res 32(8):3339–3344

    PubMed  Google Scholar 

  30. Rosell R, Molina MA, Serrano MJ (2012) EGFR mutations in circulating tumour DNA. Lancet Oncol 13(10):971–973

    Article  CAS  PubMed  Google Scholar 

  31. Maheswaran S, Sequist LV, Nagrath S et al (2008) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359(4):366–377

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr Alison Foote (Grenoble Clinical Research Centre) for critically reading and editing the manuscript with particular attention to English usage.

Conflict of interest

Denis Moro-Sibilot has consulted for Pfizer, Boehringer Ingelheim, Roche, AstraZeneca, Eli Lilly, AMGEN, Sanofi Aventis, and Novartis.

Gilbert Ferretti reports personal fees from Boehringer Ingelheim, non-financial support from Guerbet, personal fees from Intermune, personal fees from Roche, personal fees from Pfizer, personal fees from Lilly, and personal fees from Actelion, outside the submitted work.

The other authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Unité d’Oncologie Thoracique, PCMAC, CHU Grenoble France and INSERM U 823, Grenoble, France

    Cecile Bosc, François Arbib & Denis Moro-Sibilot

  2. Clinique Universitaire de Radiologie et Imagerie Médicale, Université Alpes-Grenoble, CHU Grenoble, Grenoble, France

    Gilbert R. Ferretti

  3. Service de Pneumologie Hôpital Tenon et, GRC-04 Theranoscan, Université Pierre-et-Marie Curie, Paris, France

    Jacques Cadranel

  4. Service de Pneumologie Hôpital Sainte Musse, Toulon, France

    Clarisse Audigier-Valette

  5. Departement de Médecine, Institut Gustave Roussy, Villejuif, France

    Benjamin Besse

  6. Unité Oncologie Multidisciplinaire et Innovations Thérapeutiques, Université Aix Marseille–Assistance Publique Hôpitaux de Marseille, Marseille, France

    Fabrice Barlesi

  7. Service de Pneumologie Hôpital d’Annecy, Annecy, France

    Chantal Decroisette

  8. Service d’Anatomopathologie, CHU Grenoble, Grenoble, France

    Sylvie Lantuejoul

  9. Thoracic Oncology Unit, CHU de Grenoble, CS10217-38043, Grenoble Cedex 9, France

    Denis Moro-Sibilot

Authors
  1. Cecile Bosc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gilbert R. Ferretti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jacques Cadranel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Clarisse Audigier-Valette
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Benjamin Besse
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fabrice Barlesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chantal Decroisette
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sylvie Lantuejoul
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. François Arbib
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Denis Moro-Sibilot
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Denis Moro-Sibilot.

Additional information

Gilbert R. Ferretti and François Arbib contributed equally

Electronic supplementary material

Below is the link to the electronic supplementary material.

Table A

(DOCX 13 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bosc, C., Ferretti, G.R., Cadranel, J. et al. Rebiopsy during disease progression in patients treated by TKI for oncogene-addicted NSCLC. Targ Oncol 10, 247–253 (2015). https://doi.org/10.1007/s11523-014-0332-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11523-014-0332-y

Keywords

Search

Navigation