Intrathecal trastuzumab in the management of HER2+ breast leptomeningeal disease: a single institution experience
- 294 Downloads
Leptomeningeal disease is a rare and devastating presentation of advanced stage metastatic breast cancer with historically poor overall survival. We assessed the safety and feasibility of intrathecal (IT) trastuzumab in HER2+ leptomeningeal disease.
A total of 13 patients were treated at our institution with IT trastuzumab beginning November 2012 and followed until November 2017. Outcomes including craniospinal progression as well as overall survival (OS) following initiation of IT trastuzumab were assessed from review of the clinical chart and radiologic examinations.
The median age of patients was 48 (range 29–75). Median time from breast cancer diagnosis to development of brain metastases was 87.7 months with a median of 4.6 months from brain metastases diagnosis to the development of leptomeningeal disease. Previous whole brain radiotherapy was received by the majority of patients (92%) and prior surgery for brain metastases was performed in 23%. Median duration of IT trastuzumab treatment was 6.4 months. Median time from IT trastuzumab start to craniospinal progression was 5.7 months with 6- and 12-month Kaplan–Meier rates of 41 and 21%, respectively. Sustained responses > 6 months were achieved in 4 patients. Median survival from the start of IT trastuzumab was 10.6 months with 6- and 12-month OS rates of 68 and 47%, respectively. IT trastuzumab was well tolerated with one patient developing ventriculitis, which resolved with IV antibiotics.
IT trastuzumab was well tolerated with prolongation of OS over historical controls. IT trastuzumab should be considered for management of HER2+ leptomeningeal disease patients.
KeywordsIntrathecal trastuzumab Intrathecal herceptin HER2+ breast cancer Leptomeningeal disease
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflicts of interest.
- 1.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 CrossRefPubMedGoogle 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 CrossRefPubMedGoogle Scholar
- 5.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 Neurooncol 113:83–92. https://doi.org/10.1007/s11060-013-1092-8 CrossRefPubMedGoogle Scholar
- 6.Mittica G, Senetta R, Richiardi L, Ruda R, Coda R, Castellano I, Sapino A, Cassoni P (2015) Meningeal carcinomatosis underdiagnosis and overestimation: incidence in a large consecutive and unselected population of breast cancer patients. BMC Cancer 15:1021. https://doi.org/10.1186/s12885-015-2042-y CrossRefPubMedPubMedCentralGoogle Scholar
- 7.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 CrossRefPubMedGoogle Scholar
- 8.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 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.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 CrossRefPubMedGoogle Scholar
- 14.Stemmler HJ, Schmitt M, Willems A, Bernhard H, Harbeck N, Heinemann V (2007) Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier. Anticancer Drugs 18:23–28. https://doi.org/10.1097/01.cad.0000236313.50833.ee CrossRefPubMedGoogle Scholar
- 15.Cao Y, Tsien CI, Shen Z, Tatro DS, Ten Haken R, Kessler ML, Chenevert TL, Lawrence TS (2005) Use of magnetic resonance imaging to assess blood-brain/blood-glioma barrier opening during conformal radiotherapy. J Clin Oncol 23:4127–4136. https://doi.org/10.1200/JCO.2005.07.144 CrossRefPubMedGoogle Scholar
- 16.Mego M, Sycova-Mila Z, Obertova J, Rajec J, Liskova S, Palacka P, Porsok S, Mardiak J (2011) Intrathecal administration of trastuzumab with cytarabine and methotrexate in breast cancer patients with leptomeningeal carcinomatosis. Breast 20:478–480. https://doi.org/10.1016/j.breast.2011.05.007 CrossRefPubMedGoogle Scholar
- 17.Stemmler HJ, Mengele K, Schmitt M, Harbeck N, Laessig D, Herrmann KA, Schaffer P, Heinemann V (2008) Intrathecal trastuzumab (herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: a case report. Anticancer Drugs 19:832–836. https://doi.org/10.1097/CAD.0b013e32830b58b0 CrossRefPubMedGoogle Scholar
- 18.Chamberlain M, Junck L, Brandsma D, Soffietti R, Ruda R, Raizer J, Boogerd W, Taillibert S, Groves MD, Le Rhun E, Walker J, van den Bent M, Wen PY, Jaeckle KA (2017) Leptomeningeal metastases: a RANO proposal for response criteria. Neuro-Oncology 19:484–492. https://doi.org/10.1093/neuonc/now183 CrossRefPubMedGoogle Scholar