Skip to main content
SpringerLink
Log in

Efficacy of Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer with Leptomeningeal Metastases Pretreated with EGFR-Tyrosine Kinase Inhibitors

  • Short Communication
  • Published:
Targeted Oncology Aims and scope Submit manuscript

Abstract

Background

The prognosis of patients with non-small cell lung cancer (NSCLC) who develop leptomeningeal metastasis (LM) is poor.

Objective

To assess the clinical efficacy of osimertinib, a third-generation tyrosine-kinase inhibitor (TKI), in patients with epidermal growth-factor receptor (EGFR)-mutated NSCLCs and LM.

Patients and Methods

Retrospective study of NSCLC patients with osimertinib-treated EGFR-mutated NSCLC and LM.

Results

Twenty patients (mean age, 61.2 years; 70% women) with adenocarcinoma NSCLC were included in the study. EGFR mutations were reported in exons 18 (n = 2), 19 (n = 7), and 21 (n = 11). Before starting osimertinib, patients had received a mean of 2.3 treatment lines. When LM was diagnosed, all patients had clinical symptoms. Sixteen (80%) patients had a performance status ≥2. At osimertinib initiation, 13 (65%) patients harbored the EGFR-T790M–resistance mutation. Osimertinib was started at 80 (n = 17), 160 (n = 2), or 40 mg/day (n = 1). All 13 (100%) patients with the T790M mutation and 4 (57%) of those without it obtained clinical responses. Among the 11 radiologically assessable patients, 9 (82%) responded, with 5 responses reported within 15 days after treatment initiation. Median overall survival and progression-free survival were 18.0 and 17.2 months, respectively, from the start of osimertinib.

Conclusions

In this non-selected population, osimertinib had remarkable efficacy in NSCLC patients with LM irrespective of the presence of the EGFR-T790M–resistance mutation. Osimertinib efficacy was rapid in several patients, even some with poor performance status.

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

References

  1. Nan X, Xie C, Yu X, Liu J. EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer. Oncotarget. 2017;8:75712–26.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Gazdar AF. Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene. 2009;28(Suppl 1):S24–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Janne PA, Johnson BE. Effect of epidermal growth factor receptor tyrosine kinase domain mutations on the outcome of patients with non-small cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors. Clin Cancer Res. 2006;12:4416s–20s.

    Article  PubMed  Google Scholar 

  4. Mazza V, Cappuzzo F. Treating EGFR mutation resistance in non-small cell lung cancer – role of osimertinib. Appl Clin Genet. 2017;10:49–56.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Janne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, et al. AZD9291 in EGFR inhibitor-resistant non-small–cell lung cancer. N Engl J Med. 2015;372:1689–99.

    Article  PubMed  Google Scholar 

  6. Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, et al. Osimertinib or platinum–pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376:629–40.

    Article  PubMed  CAS  Google Scholar 

  7. Goss G, Tsai CM, Shepherd FA, Bazhenova L, Lee JS, Chang GC, et al. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2016;17:1643–52.

    Article  PubMed  CAS  Google Scholar 

  8. Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B. Lee KH, et al. osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378:113–25.

    Article  PubMed  Google Scholar 

  9. Gleissner B, Chamberlain MC. Neoplastic meningitis. Lancet Neurol. 2006;5:443–52.

    Article  PubMed  Google Scholar 

  10. Remon J, Le Rhun E, Besse B. Leptomeningeal carcinomatosis in non-small cell lung cancer patients: a continuing challenge in the personalized treatment era. Cancer Treat Rev. 2017;53:128–37.

    Article  PubMed  CAS  Google Scholar 

  11. Liao BC, Lee JH, Lin CC, Chen YF, Chang CH, Ho CC, et al. Epidermal growth factor receptor tyrosine kinase inhibitors for non-small-cell lung cancer patients with leptomeningeal carcinomatosis. J Thorac Oncol. 2015;10:1754–61.

    Article  PubMed  CAS  Google Scholar 

  12. Li YS, Jiang BY, Yang JJ, Tu HY, Zhou Q, Guo WB, et al. Leptomeningeal metastases in patients with NSCLC with EGFR mutations. J Thorac Oncol. 2016;11:1962–9.

    Article  PubMed  Google Scholar 

  13. Kuiper JL, Hendriks LE, van der Wekken AJ, de Langen AJ, Bahce I, Thunnissen E, et al. Treatment and survival of patients with EGFR-mutated non-small cell lung cancer and leptomeningeal metastasis: a retrospective cohort analysis. Lung Cancer. 2015;89:255–61.

    Article  PubMed  Google Scholar 

  14. Ballard P, Yates JW, Yang Z, Kim DW, Yang JC, Cantarini M, et al. Preclinical comparison of osimertinib with other EGFR-TKIs in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity. Clin Cancer Res. 2016;22:5130–40.

    Article  PubMed  CAS  Google Scholar 

  15. Nanjo S, Ebi H, Arai S, Takeuchi S, Yamada T, Mochizuki S, et al. High efficacy of third generation EGFR inhibitor AZD9291 in a leptomeningeal carcinomatosis model with EGFR-mutant lung cancer cells. Oncotarget. 2016;7:3847–56.

    Article  PubMed  Google Scholar 

  16. Tan CS, Cho BC, Soo RA. Treatment options for EGFR mutant NSCLC with CNS involvement – can patients BLOOM with the use of next generation EGFR TKIs? Lung Cancer. 2017;108:29–37.

    Article  PubMed  Google Scholar 

  17. Berger LA, Riesenberg H, Bokemeyer C. Atanackovic D. CNS metastases in non-small-cell lung cancer: current role of EGFR-TKI therapy and future perspectives. Lung Cancer. 2013;80:242–8.

    Article  PubMed  Google Scholar 

  18. Glass JP, Melamed M, Chernik NL, Posner JB. Malignant cells in cerebrospinal fluid (CSF): the meaning of a positive CSF cytology. Neurology. 1979;29:1369–75.

    Article  PubMed  CAS  Google Scholar 

  19. Umemura S, Tsubouchi K, Yoshioka H, Hotta K, Takigawa N, Fujiwara K, et al. Clinical outcome in patients with leptomeningeal metastasis from non-small cell lung cancer: Okayama lung Cancer study group. Lung Cancer. 2012;77:134–9.

    Article  PubMed  Google Scholar 

  20. Hyun JW, Jeong IH, Joung A, Cho HJ, Kim SH, Kim HJ. Leptomeningeal metastasis: clinical experience of 519 cases. Eur J Cancer. 2016;56:107–14.

    Article  PubMed  Google Scholar 

  21. Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crino L, et al. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018;29(3):687–93.

    Article  PubMed  CAS  Google Scholar 

  22. Nanjo S, Hata A, Okuda C, Kaji R, Okada H, Tamura D, et al. Standard-dose osimertinib for refractory leptomeningeal metastases in T790M-positive EGFR-mutant non-small cell lung cancer. Br J Cancer. 2018;118:32–7.

    Article  PubMed  CAS  Google Scholar 

  23. Hochmair M. Medical treatment options for patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer suffering from brain metastases and/or leptomeningeal disease. Target Oncol. 2018. https://doi.org/10.1007/s11523-018-0566-1.

Download references

Author information

Authors and Affiliations

  1. Pneumologie et Oncologie Thoracique, CH François-Quesnay, 2, Boulevard de Sully, 78200, Mantes-la-Jolie, France

    Karima Saboundji & Jean-Bernard Auliac

  2. Oncologie, Centre Léon-Bérard, Lyon, France

    Maurice Pérol

  3. Pneumologie et Oncologie Thoracique, CHU d’Amiens, Amiens, France

    Géraldine François

  4. Pneumologie, CHU Clermont-Ferrand, Clermont-Ferrand, France

    Henri Janicot

  5. Pneumologie, CHU Vendée, La Roche-sur-Yon, France

    Marie Marcq

  6. Oncologie, Centre François-Baclesse, Caen, France

    Catherine Dubos-Arvis & Radj Gervais

  7. Pneumologie, CH François-Mitterrand, Pau, France

    Aldo Renault

  8. Pneumologie, CHU Charles-Nicolle, Rouen, France

    Florian Guisier

  9. Pneumologie, Hôpital Nord-Ouest, Villefranche-sur-Saône, France

    Luc Odier

  10. Pneumologie, CH Intercommunal de Créteil, Créteil, France

    Christos Chouaïd

Authors
  1. Karima Saboundji
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jean-Bernard Auliac
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maurice Pérol
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Géraldine François
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Henri Janicot
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marie Marcq
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Catherine Dubos-Arvis
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Aldo Renault
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Florian Guisier
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Luc Odier
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Radj Gervais
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Christos Chouaïd
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jean-Bernard Auliac.

Ethics declarations

Funding

No external funding was used in the preparation of this manuscript.

Conflicts of Interest

K. Saboundji: fees to attend scientific meetings (Astra-Zeneca). J.-B. Auliac: fees to attend scientific meetings, speak, organize research or consult from Boehringer-Ingelheim, Hoffman-Roche, MSD, Bristol-Myers Squibb and Pfizer. M. Pérol: Roche, Genentech, Eli Lilly, Pfizer, Boehringer-Ingelheim, Clovis Oncology, MSD, Bristol-Myers Squibb, Novartis, Pierre Fabre, Astra-Zeneca (Advisory Boards); Roche, Astra-Zeneca, Chugai (institutional grants); Eli Lilly, Roche, Astra-Zeneca, Pfizer, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Takeda (scientific meetings). A. Renault: Astra-Zeneca, Bristol-Myers Squibb, Novartis and Lilly. L. Odier: Lilly (Advisory Board), Pfizer (scientific meeting) and Amgen (scientific meeting). R. Gervais: fees for scientific meetings or advisory boards for Astra-Zeneca, Roche and Boehringer-Ingelheim. C. Chouaïd: fees to attend scientific meetings, speak, organize research or consult from Astra-Zeneca, Boehringer-Ingelheim, Roche and Clovis. G. François, H. Janicot, M. Marcq, C. Dubos-Arvis, and F. Guisier declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saboundji, K., Auliac, JB., Pérol, M. et al. Efficacy of Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer with Leptomeningeal Metastases Pretreated with EGFR-Tyrosine Kinase Inhibitors. Targ Oncol 13, 501–507 (2018). https://doi.org/10.1007/s11523-018-0581-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11523-018-0581-2

Search

Navigation