Skip to main content

Advertisement

SpringerLink
Log in

Clinical outcomes in patients who received lapatinib plus capecitabine combination therapy for HER2-positive breast cancer with brain metastasis and a comparison of survival with those who received trastuzumab-based therapy: a study by the Anatolian Society of Medical Oncology

  • Original Article
  • Published:
Breast Cancer Aims and scope Submit manuscript

Abstract

Purpose

In this study, we investigated the effect of lapatinib plus capecitabine treatment in HER2-positive breast cancer patients with brain metastasis.

Methods

Of 405 metastatic breast cancer patients with brain metastases at referral centers in Turkey, 46 were treated with lapatinib plus capecitabine only after the development of brain metastasis. Patients who only received trastuzumab-based therapy after the development of brain metastases were accepted as the historic control group for survival analyses (n = 65). Patients who received both drugs consecutively or sequentially were excluded from the analyses (n = 34).

Results

Median age among 46 patients who received lapatinib plus capecitabine therapy was 45 years (27–76), and median time for development of brain metastases was 11.9 months (0–69 months). Twenty-six out of 38 patients who received lapatinib plus capecitabine and had extracranial metastasis showed partial response or stable diseases (68.4 %). Grade 3-4 toxicity was observed in eight patients (17.3 %). Median overall survival (OS) in patients treated with lapatinib plus capecitabine was significantly increased compared to that in patients treated with trastuzumab-based therapy (19.1 vs. 12 months, respectively, p = 0.039). The incidence of cerebral death was slightly decreased in patients who received lapatinib plus capecitabine compared to those who received trastuzumab-based therapy (32 vs. 43.4 %, p = 0.332). In the multivariate analysis, lapatinib plus capecitabine therapy remained an independent positive predictor for survival [odds ratio (OR), 0.57; p = 0.02].

Discussion

Although this retrospective multicenter study had several limitations, the results suggest that undergoing lapatinib plus capecitabine therapy after the diagnosis of brain metastasis may further improve survival compared to undergoing only trastuzumab-based therapy.

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

Similar content being viewed by others

References

  1. Lin N, Bellon J, Winer E. CNS metastases in breast cancer. J Clin Oncol. 2004;22:3608–17.

    Article  PubMed  Google Scholar 

  2. Tomasello G, Bedard PL, de Azambuja E, Lossignol D, Devriendt D, Piccart-Gebhart MJ. Brain metastases in HER2-positive breast cancer: the evolving role of lapatinib. Crit Rev Oncol Hematol. 2010;75(2):110–21.

    Article  PubMed  Google Scholar 

  3. Cheng X, Hung MC. Breast cancer brain metastases. Cancer Metastasis Rev. 2007;26(3–4):635–43. (review).

    Article  PubMed  Google Scholar 

  4. Sjögren S, Inganäs M, Lindgren A, Holmberg L, Bergh J. Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers. J Clin Oncol. 1998;16:462–9.

    PubMed  Google Scholar 

  5. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–82.

    Article  PubMed  CAS  Google Scholar 

  6. Owens MA, Horten BC, Da Silva MM. HER2- amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6,556 breast cancer tissues. Clin Breast Cancer. 2004;5:63–9.

    Article  PubMed  CAS  Google Scholar 

  7. Leyland-Jones B. Human epidermal growth factor receptor 2-positive breast cancer and central nervous system metastases. J Clin Oncol. 2009;27(31):5278–86. (review).

    Article  PubMed  Google Scholar 

  8. Weil R, Palmieri D, Bronder J, Stark A, Steeg P. Breast cancer metastasis to the central nervous system. Am J Pathol. 2005;167(4):913–20.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  9. Soffietti R, Ruda R, Trevisan E. Brain metastases: current management and new developments. Curr Opin Oncol. 2008;20:676–84.

    Article  PubMed  Google Scholar 

  10. Niwińska A, Murawska M, Pogoda K. Breast cancer brain metastases: differences in survival depending on biological subtype, RPA RTOG prognostic class and systemic treatment after whole-brain radiotherapy (WBRT). Ann Oncol. 2010;21(5):942–8.

    Article  PubMed  Google Scholar 

  11. Arslan UY, Oksuzoglu B, Aksoy S, et al. Breast cancer subtypes and outcomes of central nervous system metastases. Breast. 2011;20(6):562–7.

    Article  PubMed  Google Scholar 

  12. Kim HJ, Im SA, Keam B, et al. Clinical outcome of central nervous system metastases from breast cancer: differences in survival depending on systemic treatment. J Neurooncol. 2012;106(2):303–13.

    Article  PubMed  Google Scholar 

  13. Sutherland S, Ashley S, Miles D, et al. Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases–the UK experience. Br J Cancer. 2010;102(6):995–1002.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Lin NU, Diéras V, Paul D, et al. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res. 2009;15(4):1452–9.

    Article  PubMed  CAS  Google Scholar 

  15. Bartsch R, Rottenfusser A, Wenzel C, et al. Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer. J Neurooncol. 2007;85(3):311–7.

    Article  PubMed  CAS  Google Scholar 

  16. Bartsch R, Berghoff A, Pluschnig U, et al. Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases. Br J Cancer. 2012;106(1):25–31. doi:10.1038/bjc.2011.531.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Metro G, Foglietta J, Russillo M, et al. Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine. Ann Oncol. 2011;22(3):625–30.

    Article  PubMed  CAS  Google Scholar 

  18. Gril B, Palmieri D, Bronder JL, et al. Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain. J Natl Cancer Inst. 2008;100(15):1092–103.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.

    Article  PubMed  CAS  Google Scholar 

  20. Burstein HJ, Kuter I, Campos SM, et al. Clinical activity of trastuzumab and vinorelbin in women with HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2001;19:2722–30.

    PubMed  CAS  Google Scholar 

  21. Kuzur ME, Albain KS, Huntington MO, et al. A phase II trial of docetaxel and herceptin in metastatic breast cancer patients overexpressing HER-2. Proc Am Soc Clin Oncol. 2000;19:131a.

    Google Scholar 

  22. Pestalozzi BC, Brignoli S. Trastuzumab in CSF. J Clin Oncol. 2000;18:2349–51.

    PubMed  CAS  Google Scholar 

  23. Pinder MC, Chang H, Broglio KR, et al. Trastuzumab treatment and the risk of central nervous system (CNS) metastases. J Clin Oncol. 2007;25:36s.

    Article  Google Scholar 

  24. Park YH, Park MJ, Ji SH, et al. Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients. Br J Cancer. 2009;100:894–900.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Pivot X, Semiglazov V, Zurawski B, Allerton R, Fabi A, Ciruleos E, Parikh R, Desilvio, Santillana S, Swaby R. CEREBEL (EGF111438): an open label randomized phase III study comparing the incidence of CNS metastases in patients (pts) with HER2+ Metastatic Breast Cancer (MBC), treated with Lapatinib plus Capecitabine (LC) versus Trastuzumab plus Capecitabine (TC). 37th ESMO Congress. Late Braking Abstract 11, Vienna, Austuria (2012).

  26. Takano T, Kimura H, Hishio K, Yamanaka T, Ito Y, Fukuoka J, et al. WJOG6110B (ELTOP): randomized phase II trial comparing trastuzumab plus capecitabin (HX) and lapatinib plus capecitabin (LX) in HER2-positive metastatic breast cancer patients previously treated with trastuzumab and taxanes. J Clin Oncol. 2012;30(suppl):abstr TPS659.

  27. Niwińska A, Tacikowska M, Murawska M. The effect of early detection of occult brain metastases in HER2-positive breast cancer patients on survival and cause of death. Int J Radiat Oncol Biol Phys. 2010;77(4):1134–9.

    Article  PubMed  Google Scholar 

  28. Hall WA, Djalilian HR, Nussbaum ES, Cho KH. Long-term survival with metastatic cancer to the brain. Med Oncol. 2000;17:279–86.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Dicle University School of Medicine, 21280, Diyarbakir, Turkey

    Muhammet Ali Kaplan, Abdurrahman Isikdogan, Mehmet Kucukoner, Ali İnal & Zuhat Urakci

  2. Department of Medical Oncology, Dokuz Eylul University School of Medicine, Izmir, Turkey

    Doğan Koca, Adem Dayan & Tulay Akman

  3. Department of Medical Oncology, Gazi University School of Medicine, Ankara, Turkey

    Ozge Gumusay & Ugur Coskun

  4. Department of Medical Oncology, Dr. Lutfi Kırdar Kartal Training and Research Hospital, Istanbul, Turkey

    Ramazan Yildiz & Nur Sener

  5. Department of Medical Oncology, Ankara Oncology Training and Research Hospital-2, Ankara, Turkey

    Ulku Yalcintas Arslan & Berna Oksuzoglu

  6. Department of Medical Oncology, Ankara Oncology Training and Research Hospital-1, Ankara, Turkey

    Ayse Gok Durnalı

  7. Department of Medical Oncology, Izmir Ataturk Training and Research Hospital, Izmir, Turkey

    Lütfiye Demir & Mustafa Oktay Tarhan

  8. Department of Medical Oncology, Selcuk University School of Medicine, Konya, Turkey

    Caglayan Geredeli & Cem Boruban

  9. Department of Medical Oncology, Suleyman Demirel University School of Medicine, Isparta, Turkey

    Murat Kocer

  10. Department of Medical Oncology, Erciyes University School of Medicine, Kayseri, Turkey

    Mevlude Inanc

  11. Department of Medical Oncology, Gaziantep University School of Medicine, Gaziantep, Turkey

    Ali Suner

  12. Department of Medical Oncology, Göztepe Medical Park Hospital, Ankara, Turkey

    Suleyman Alici

  13. Department of Medical Oncology, Ankara Numune Training and Research Hospital, Ankara, Turkey

    Nuriye Yildirim Ozdemir

  14. Department of Medical Oncology, Inonu University School of Medicine, Malatya, Turkey

    Emin Tamer Elkiran

Authors
  1. Muhammet Ali Kaplan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdurrahman Isikdogan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Doğan Koca
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mehmet Kucukoner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ozge Gumusay
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ramazan Yildiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Adem Dayan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lütfiye Demir
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Caglayan Geredeli
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Murat Kocer
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ulku Yalcintas Arslan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ali İnal
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tulay Akman
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ugur Coskun
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Nur Sener
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Mevlude Inanc
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Emin Tamer Elkiran
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Nuriye Yildirim Ozdemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Ayse Gok Durnalı
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Ali Suner
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Suleyman Alici
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Mustafa Oktay Tarhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Cem Boruban
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Berna Oksuzoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Zuhat Urakci
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Muhammet Ali Kaplan.

Additional information

This study was performed by ASMO and was accepted as an abstract in ASCO 2012.

About this article

Cite this article

Kaplan, M.A., Isikdogan, A., Koca, D. et al. Clinical outcomes in patients who received lapatinib plus capecitabine combination therapy for HER2-positive breast cancer with brain metastasis and a comparison of survival with those who received trastuzumab-based therapy: a study by the Anatolian Society of Medical Oncology. Breast Cancer 21, 677–683 (2014). https://doi.org/10.1007/s12282-013-0441-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12282-013-0441-y

Keywords

Search

Navigation