Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Case report

Efficacy of T-DM1 for leptomeningeal and brain metastases in a HER2 positive metastatic breast cancer patient: new directions for systemic therapy - a case report and literature review

Authors: Giuseppina Rosaria Rita Ricciardi, Alessandro Russo, Tindara Franchina, Silvia Schifano, Giampiero Mastroeni, Anna Santacaterina, Vincenzo Adamo

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

Herein, we report a complete response after whole brain radiotherapy (WBRT) and concomitant T-DM1 in a patient with HER2-positive metastatic breast cancer (MBC) and extensive brain and leptomeningeal involvement.

Case presentation

A 46 years old Caucasian woman with HER2-positive MBC and no baseline CNS involvement, started in August 2015 1st line therapy with Pertuzumab-Trastuzumab-Docetaxel, with partial response. However, in April 2016 the patient eventually progressed with emergence of brain and leptomeningeal metastases. Hence, she started in May 2016 2nd line therapy with T-DM1 and concomitant WBRT, with complete response (CR) after 3 courses of therapy, with complete resolution of neurological symptoms and no relevant toxicities. The CR is lasting over 13 months and the patient is out of corticosteroid use.

Conclusions

To the best of our knowledge, this is the first case reporting interesting antitumor activity of T-DM1 and concomitant WBRT in both brain and leptomeningeal metastases, with a favorable safety profile and prolonged extracranial disease control. Further prospective studies should confirm these findings.
Literature
1.
Loibl S, Gianni L. HER2-positive breast cancer. Lancet. 2017;389(10087):2415-2429.
2.
Mehta AI, Brufsky AM, Sampson JH. Therapeutic approaches for HER2-positive brain metastases: circumventing the blood-brain barrier. Cancer Treat Rev. 2013;39(3):261–9.CrossRefPubMed
3.
Lin NU, Amiri-Kordestani L, Palmieri D, Liewehr DJ, Steeg PS. CNS metastases in breast cancer: old challenge, new frontiers. Clin Cancer Res. 2013;19(23):6404–18.CrossRefPubMed
4.
Morikawa A, Jordan L, Rozner R, Patil S, Boire A, Pentsova E, et al. Characteristics and outcomes of patients with breast cancer with Leptomeningeal metastasis. Clin Breast Cancer. 2017;17(1):23–8.CrossRefPubMed
5.
Le Rhun E, Taillibert S, Zairi F, Kotecki N, Devos P, Mailliez A, et al. A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer. J Neuro-Oncol. 2013;113(1):83–92.CrossRef
6.
Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(6):732–42.CrossRefPubMed
7.
Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Crnjevic T, et al. Trastuzumab emtansine versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial. Lancet Oncol. 2017;18(6):743–54.CrossRefPubMed
8.
Krop IE, Lin NU, Blackwell K, Guardino E, Huober J, Lu M, et al. Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA. Ann Oncol. 2015;26(1):113–9.CrossRefPubMed
9.
Bartsch R, Berghoff AS, Preusser M. Breast cancer brain metastases responding to primary systemic therapy with T-DM1. J Neuro-Oncol. 2014;116(1):205–6.CrossRef
10.
Torres S, Maralani P, Verma S. Activity of T-DM1 in HER-2 positive central nervous system breast cancer metastases. BMJ Case Rep. 2014;2014.
11.
Kalsi R, Feigenberg S, Kwok Y, Tkaczuk K, Mehta M, Chumsri S. Brain metastasis and response to ado-trastuzumab emtansine: a case report and literature review. Clin Breast Cancer. 2015;15(2):e163–6.CrossRefPubMed
12.
Keith KC, Lee Y, Ewend MG, Zagar TM, Anders CK. Activity of Trastuzumab Emtansine (TDM1) in HER2-positive breast cancer brain metastases: a case series. Cancer Treat Commun. 2016;7:43–6.
13.
Bartsch R, Berghoff AS, Vogl U, Rudas M, Bergen E, Dubsky P, et al. Activity of T-DM1 in Her2-positive breast cancer brain metastases. Clin Exp Metastasis. 2015;32(7):729–37.CrossRefPubMed
14.
Jacot W, Pons E, Frenel JS, Guiu S, Levy C, Heudel PE, et al. Efficacy and safety of trastuzumabemtansine (T-DM1) in patients with HER2-positive breast cancer with brain metastases. Breast Cancer Res Treat. 2016;157(2):307–18.CrossRefPubMed
15.
Venur VA, Ahluwalia MS. Targeted therapy in brain metastases: ready for primetime? Am Soc Clin Oncol Educ Book. 2016;35:e123–30.CrossRefPubMed
16.
Fontanella C, De Carlo E, Cinausero M, Pelizzari G, Venuti I, Puglisi F. Central nervous system involvement in breast cancer patients: is the therapeutic landscape changing too slowly? Cancer Treat Rev. 2016;46:80–8.CrossRefPubMed
17.
Phillips C, Jeffree R, Khasraw M. Management of breast cancer brain metastases: a practical review. Breast. 2017;31:90–8.CrossRefPubMed
18.
Chamberlain MC, Baik CS, Gadi VK, Bhatia S, Chow LQ. Systemic therapy of brain metastases: non-small cell lung cancer, breast cancer, and melanoma. Neuro-Oncology. 2017;19(1):i1–i24.CrossRefPubMed
19.
Murrell DH, Foster PJ, Chambers AF. Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications. J Mol Med (Berl). 2014;92(1):5–12.CrossRef
20.
Adkins CE, Mohammad AS, Terrell-Hall TB, Dolan EL, Shah N, Sechrest E, et al. Characterization of passive permeability at the blood-tumor barrier in five preclinical models of brain metastases of breast cancer. Clin Exp Metastasis. 2016;33(4):373–83.CrossRefPubMedPubMedCentral
21.
Lockman PR, Mittapalli RK, Taskar KS, Rudraraju V, Gril B, Bohn KA, et al. Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer. Clin Cancer Res. 2010;16(23):5664–78.CrossRefPubMedPubMedCentral
22.
vanVulpen M, Kal HB, Taphoorn MJ, El-Sharouni SY. Changes in blood-brain barrier permeability induced by radiotherapy: implications for timing of chemotherapy? (review). Oncol Rep. 2002;9(4):683–8.
23.
Stemmler HJ, Schmitt M, Willems A, Bernhard H, Harbeck N, Heinemann V. 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. Anti-Cancer Drugs. 2007;18(1):23–8.CrossRefPubMed
24.
Dijkers EC, Oude Munnink TH, Kosterink JG, Brouwers AH, Jager PL, de Jong JR, et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 2010;87(5):586–92.CrossRefPubMed
25.
Ricciardi GR, Russo A, Franchina T, Ferraro G, Adamo V. Efficacy of nab-paclitaxel plus trastuzumab in a long-surviving heavily pretreated HER2-positive breast cancer patient with brain metastases. Onco Targets Ther. 2015;8:289–94.PubMedPubMedCentral
26.
Olson EM, Abdel-Rasoul M, Maly J, Wu CS, Lin NU, Shapiro CL. Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab. Ann Oncol. 2013;24(6):1526–33.CrossRefPubMedPubMedCentral
27.
Bartsch R, Rottenfusser A, Wenzel C, Dieckmann K, Pluschnig U, Altorjai G, et al. Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer. J Neuro-Oncol. 2007;85(3):311–7.CrossRef
28.
Rostami R, Mittal S, Rostami P, Tavassoli F, Jabbari B. Brain metastasis in breast cancer: a comprehensive literature review. J Neuro-Oncol. 2016;127(3):407–14.CrossRef
29.
Shen Q, Sahin AA, Hess KR, Suki D, Aldape KD, Sawaya R, et al. Breast cancer with brain metastases: clinicopathologic features, survival, and paired biomarker analysis. Oncologist. 2015;20(5):466–73.CrossRefPubMedPubMedCentral
30.
Chargari C, Idrissi HR, Pierga JY, Bollet MA, Diéras V, Campana F, et al. Preliminary results of whole brain radiotherapy with concurrent trastuzumab for treatment of brain metastases in breast cancer patients. Int J Radiat Oncol Biol Phys. 2011;81(3):631–6.CrossRefPubMed
31.
Lin NU, Carey LA, Liu MC, Younger J, Come SE, Ewend M, et al. Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2008;26(12):1993–9.CrossRefPubMedPubMedCentral
32.
Lin NU, Diéras V, Paul D, Lossignol D, Christodoulou C, Stemmler HJ, 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.CrossRefPubMed
33.
Boccardo F, Kaufman B, Baselga J, Dieras V, Link J, Casey MA, et al. Evaluation of lapatinib plus capecitabinein patients with brain metastases from HER2+ breast cancer enrolled in the Lapatinib expanded access program (LEAP) and French AuthorisationTemporaired’Utilisation (ATU). J Clin Oncol. 2008;26(15S Supplement):1094.CrossRef
34.
Metro G, Foglietta J, Russillo M, Stocchi L, Vidiri A, Giannarelli D, 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.CrossRefPubMed
35.
Sutherland S, Ashley S, Miles D, Chan S, Wardley A, Davidson N, 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.CrossRefPubMedPubMedCentral
36.
Bachelot T, Romieu G, Campone M, Diéras V, Cropet C, Dalenc F, et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study. Lancet Oncol. 2013;14(1):64–71.CrossRefPubMed
37.
Lin NU, Eierman W, Greil R, Campone M, Kaufman B, Steplewski K, et al. Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases. J Neuro-Oncol. 2011;105(3):613–20.CrossRef
38.
Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, et al. CEREBEL (EGF111438): a phase III, randomized, open-label study of Lapatinib plus Capecitabine versus Trastuzumab plus Capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015;33(14):1564–73.CrossRefPubMed
39.
Swain SM, Baselga J, Miles D, Im YH, Quah C, Lee LF, et al. Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: results from the randomized phase III study CLEOPATRA. Ann Oncol. 2014;25(6):1116–21.CrossRefPubMedPubMedCentral
40.
41.
Morikawa A, Peereboom DM, Thorsheim HR, Samala R, Balyan R, Murphy CG, et al. Capecitabine and lapatinib uptake in surgically resected brain metastases from metastatic breast cancer patients: a prospective study. Neuro-Oncology. 2015;17(2):289–95.CrossRefPubMed
42.
de Vries CL, Linn SC, Brandsma D. Response of symptomatic brain metastases from HER-2 overexpressing breast cancer with T-DM1. J Neuro-Oncol. 2016;127(2):401–3.CrossRef
43.
Mitsuya K, Watanabe J, Nakasu Y, Hayashi N, Harada H, Ito I. Expansive hematoma in delayed cerebral radiation necrosis in patients treated with T-DM1: a report of two cases. BMC Cancer. 2016;16:391.CrossRefPubMedPubMedCentral
44.
Carlson JA, Nooruddin Z, Rusthoven C, Elias A, Borges VF, Diamond JR, et al. Trastuzumab emtansine and stereotactic radiosurgery: an unexpected increase in clinically significant brain edema. Neuro-Oncology. 2014;16(7):1006–9.CrossRefPubMedPubMedCentral
45.
Borges GS, Rovere RK, Dias SM, Chong FH, Morais MS. Safety and efficacy of the combination of T-DM1 with radiotherapy of the central nervous system in a patient with HER2-positive metastatic breast cancer: case study and review of the literature. E Cancer Med Sci. 2015;9:586.
46.
Geraud A, Xu HP, Beuzeboc P, Kirova YM. Preliminary experience of the concurrent use of radiosurgery and T-DM1 for brain metastases in HER2-positive metastatic breast cancer. J Neuro-Oncol. 2017;131(1):69–72.CrossRef
47.
Zagar TM, Van Swearingen AE, Kaidar-Person O, Ewend MG, Anders CK. Multidisciplinary Management of Breast Cancer Brain Metastases. Oncology (Williston Park). 2016;30(10):923-33.
48.
Brower JV, Saha S, Rosenberg SA, Hullett CR, Ian RH. Management of leptomeningeal metastases: prognostic factors and associated outcomes. J Clin Neurosci. 2016;27:130–7.CrossRefPubMed
49.
Borges VF, Ferrario C, Aucoin N, Falkson CI, Khan QJ, Krop IE, et al. Efficacy results of a phase 1b study of ont-380, a CNS-penetrant TKI, in combination with T-DM1 in HER2+ metastatic breast cancer (MBC), including patients (pts) with brain metastases. J Clin Oncol 34, 2016 (suppl; abstr 513).
Metadata
Title
Efficacy of T-DM1 for leptomeningeal and brain metastases in a HER2 positive metastatic breast cancer patient: new directions for systemic therapy - a case report and literature review
Authors
Giuseppina Rosaria Rita Ricciardi
Alessandro Russo
Tindara Franchina
Silvia Schifano
Giampiero Mastroeni
Anna Santacaterina
Vincenzo Adamo
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-3994-5

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue

Research article

From symptom discovery to treatment - women's pathways to breast cancer care: a cross-sectional study

Research article

Development of a computational promoter with highly efficient expression in tumors

Research article

Impact of CDX2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis

Case report

Effective osimertinib treatment in a patient with discordant T790 M mutation detection between liquid biopsy and tissue biopsy

Research article

Resveratrol induces autophagy-dependent apoptosis in HL-60 cells

Research article

Relationship between the extent of resection and the survival of patients with low-grade gliomas: a systematic review and meta-analysis
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits