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Clinical outcomes of breast leptomeningeal disease treated with intrathecal trastuzumab, intrathecal chemotherapy, or whole brain radiation therapy

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Abstract

Purpose

Leptomeningeal disease is a rare presentation of advanced metastatic breast cancer. The purpose of this study was to evaluate craniospinal progression between intrathecal (IT) trastuzumab, IT chemotherapy, and whole brain radiation therapy (WBRT) in leptomeningeal disease.

Methods

A total of 56 patients were identified with breast cancer leptomeningeal disease at our institution treated with IT trastuzumab (n = 18; 32%), single-agent IT chemotherapy (methotrexate n = 14 or thiotepa n = 1; 27%), or WBRT alone (n = 23; 41%). Patients were treated beginning November 2012 and followed until November 2018.

Results

Median time from breast cancer diagnosis to development of leptomeningeal disease was 4.3 years. There were no significant differences noted between IT trastuzumab, IT chemotherapy, or WBRT groups in age (p = 0.4), Karnofsky Performance Status (KPS) (p = 0.07), or receipt of systemic therapy at time of leptomeningeal disease treatment (p = 0.47). Median follow-up of patients from leptomeningeal diagnosis was 5 months (range 0.2–81.1 months). Significant differences were noted in Kaplan–Meier (KM) craniospinal progression-free survival (CS-PFS) with 6-month rates of 44%, 18%, and 26% (p = 0.04) between IT trastuzumab, IT chemotherapy, and WBRT, respectively. Craniospinal control > 10 months was achieved in four patients treated with IT trastuzumab. Twelve-month KM OS rates were 54%, 10%, and 19% (p = 0.01) between IT trastuzumab, IT chemotherapy, and WBRT groups, respectively. IT therapy was adequately tolerated with three patients undergoing treatment-related hospitalizations.

Conclusions

In our institutional series, significant differences were noted in CS-PFS and OS by treatment modality. IT trastuzumab should be considered in the management HER2+ breast leptomeningeal disease.

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References

  1. Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE (2004) Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol 22:2865–2872. https://doi.org/10.1200/JCO.2004.12.149

    Article  PubMed  Google Scholar 

  2. Bendell JC, Domchek SM, Burstein HJ, Harris L, Younger J, Kuter I, Bunnell C, Rue M, Gelman R, Winer E (2003) Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 97:2972–2977. https://doi.org/10.1002/cncr.11436 doi

    Article  PubMed  Google Scholar 

  3. Bonneau C, Paintaud G, Tredan O, Dubot C, Desvignes C, Dieras V, Taillibert S, Tresca P, Turbiez I, Li J, Passot C, Mefti F, Mouret-Fourme E, Le Rhun E, Gutierrez M (2018) Phase I feasibility study for intrathecal administration of trastuzumab in patients with HER2 positive breast carcinomatous meningitis. Eur J Cancer 95:75–84. https://doi.org/10.1016/j.ejca.2018.02.032

    Article  CAS  PubMed  Google Scholar 

  4. Bousquet G, Darrouzain F, de Bazelaire C, Ternant D, Barranger E, Winterman S, Madelaine-Chambin I, Thiebaut JB, Polivka M, Paintaud G, Culine S, Janin A (2016) Intrathecal trastuzumab halts progression of CNS metastases in breast cancer. J Clin Oncol 34:e151–e155. https://doi.org/10.1200/JCO.2012.44.8894

    Article  PubMed  Google Scholar 

  5. Brosnan EM, Anders CK (2018) Understanding patterns of brain metastasis in breast cancer and designing rational therapeutic strategies. Ann Transl Med 6:163. https://doi.org/10.21037/atm.2018.04.35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Figura NB, Long W, Yu M, Robinson TJ, Mokhtari S, Etame AB, Tran ND, Diaz R, Soliman H, Han HS, Sahebjam S, Forsyth PA, Ahmed KA (2018) Intrathecal trastuzumab in the management of HER2 + breast leptomeningeal disease: a single institution experience. Breast Cancer Res Treat 169:391–396. https://doi.org/10.1007/s10549-018-4684-3

    Article  CAS  PubMed  Google Scholar 

  7. Kumthekar P, Gradishar W, Lin N, Pentsova E, Groves M, Jeyapalan S, Melisko M, Grimm S, Lassman AB, Raizer J (2018) Intrathecal (IT) trastuzumab (T) for the treatment of leptomeningeal metastases (LM) in patients (Pts) with human epidermal growth factor receptor 2-positive (HER2+) cancer: a multicenter phase 1/2 study. Neuro-oncology 20:Vi58

    Article  Google Scholar 

  8. Le Rhun E, Taillibert S, Zairi F, Kotecki N, Devos P, Mailliez A, Servent V, Vanlemmens L, Vennin P, Boulanger T, Baranzelli MC, Andre C, Marliot G, Cazin JL, Dubois F, Assaker R, Bonneterre J, Chamberlain MC (2013) A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer. J Neuro-oncol 113:83–92. https://doi.org/10.1007/s11060-013-1092-8

    Article  Google Scholar 

  9. Lin NU, Bellon JR, Winer EP (2004) CNS metastases in breast cancer. J Clin Oncol 22:3608–3617. https://doi.org/10.1200/JCO.2004.01.175

    Article  PubMed  Google Scholar 

  10. Lu NT, Raizer J, Gabor EP, Liu NM, Vu JQ, Slamon DJ, Barstis JL (2015) Intrathecal trastuzumab: immunotherapy improves the prognosis of leptomeningeal metastases in HER-2 + breast cancer patient. J Immunother Cancer 3:41. https://doi.org/10.1186/s40425-015-0084-y

    Article  PubMed  PubMed Central  Google Scholar 

  11. Mir O, Ropert S, Alexandre J, Lemare F, Goldwasser F (2008) High-dose intrathecal trastuzumab for leptomeningeal metastases secondary to HER-2 overexpressing breast cancer. Ann Oncol 19:1978–1980. https://doi.org/10.1093/annonc/mdn654

    Article  CAS  PubMed  Google Scholar 

  12. Nayar G, Ejikeme T, Chongsathidkiet P, Elsamadicy AA, Blackwell KL, Clarke JM, Lad SP, Fecci PE (2017) Leptomeningeal disease: current diagnostic and therapeutic strategies. Oncotarget 8:73312–73328. https://doi.org/10.18632/oncotarget.20272

    Article  PubMed  PubMed Central  Google Scholar 

  13. Park WY, Kim HJ, Kim K, Bae SB, Lee N, Lee KT, Won JH, Park HS, Lee SC (2016) Intrathecal Trastuzumab Treatment in Patients with Breast Cancer and Leptomeningeal Carcinomatosis. Cancer Res Treat 48:843–847. https://doi.org/10.4143/crt.2014.234

    Article  CAS  PubMed  Google Scholar 

  14. Pestalozzi BC, Brignoli S (2000) Trastuzumab in CSF. J Clin Oncol 18:2349–2351. https://doi.org/10.1200/JCO.2000.18.11.2349

    Article  CAS  PubMed  Google Scholar 

  15. Scott BJ, Oberheim-Bush NA, Kesari S (2016) Leptomeningeal metastasis in breast cancer—a systematic review. Oncotarget 7:3740–3747. https://doi.org/10.18632/oncotarget.5911

    Article  PubMed  Google Scholar 

  16. Stemmler HJ, Schmitt M, Harbeck N, Willems A, Bernhard H, Lassig D, Schoenberg S, Heinemann V (2006) Application of intrathecal trastuzumab (Herceptintrade mark) for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer. Oncol Rep 15:1373–1377

    CAS  PubMed  Google Scholar 

  17. Tsukada Y, Fouad A, Pickren JW, Lane WW (1983) Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer 52:2349–2354

    Article  CAS  PubMed  Google Scholar 

  18. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ, Press M (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20:719–726. https://doi.org/10.1200/JCO.2002.20.3.719

    Article  CAS  PubMed  Google Scholar 

  19. Witzel I, Oliveira-Ferrer L, Pantel K, Muller V, Wikman H (2016) Breast cancer brain metastases: biology and new clinical perspectives. Breast Cancer Res 18:8. https://doi.org/10.1186/s13058-015-0665-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M (2013) Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis. Breast Cancer Res Treat 139:13–22. https://doi.org/10.1007/s10549-013-2525-y

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, Tampa, FL, 33612, USA

    Nicholas B. Figura, Homan Mohammadi, H. Michael Yu, Timothy J. Robinson, Iman Washington, Roberto Diaz & Kamran A. Ahmed

  2. Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA

    Victoria T. Rizk

  3. Departments of Neuro Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, Tampa, FL, 33612, USA

    Brittany Evernden, Sepideh Mokhtari, Arnold B. Etame, Nam D. Tran, James Liu, Solmaz Sahebjam & Peter A. Forsyth

  4. Departments of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA

    Brian J. Czerniecki, Hatem Soliman & Hyo S. Han

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  1. Nicholas B. Figura
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Correspondence to Peter A. Forsyth or Kamran A. Ahmed.

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Figura, N.B., Rizk, V.T., Mohammadi, H. et al. Clinical outcomes of breast leptomeningeal disease treated with intrathecal trastuzumab, intrathecal chemotherapy, or whole brain radiation therapy. Breast Cancer Res Treat 175, 781–788 (2019). https://doi.org/10.1007/s10549-019-05170-7

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