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Efficacy and safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with brain metastases

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Abstract

Few data are currently available regarding the efficacy and safety of T-DM1 in breast cancer (BC) patients with unselected brain metastases (BM), since most clinical trials have excluded BM patients or have only included highly selected patients. HER2 + BC patients with BM treated with T-DM1 in 5 French centers were included in this retrospective study. Clinical management was performed according to the product guidelines. Efficacy was evaluated recording tumor response rates, progression-free (PFS) and overall survival, treatment compliance, and safety. Thirty nine patients received T-DM1, among whom 82 % presented with concomitant extra-cerebral disease. Median number of previous metastatic chemotherapy and HER2-directed targeted therapy regimens was 2 (range 0–8) and 1 (0–7), respectively. Thirty six patients had received BM loco-regional treatment (72 % whole-brain radiation therapy). After a median follow-up of 8.1 months (1.4–39.6), 24 patients had progressed (first site of progression: brain 14; meningeal 2; outside of the central nervous system 5; both intra- and extra-cerebral 3), 12 patients had died (disease progression), and 27 patients were still alive. Median number of T-DM1 cycles was 8 (1–43). There were 17 partial responses (44 %) and 6 patients achieved disease stabilization (59 % clinical benefit rate). Median PFS was 6.1 months (95 %CI 5.2–18.3), with one- and two-year PFS rates of 33 and 17 %, respectively. Treatment was well tolerated, without unexpected toxicities, treatment delay, or dose reduction. In this retrospective study, T-DM1 appeared to be an effective and well-tolerated therapeutic option in unselected HER2 + BC patients with BM. These findings require a prospective validation.

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Acknowledgments

We are grateful to Dr H. de Forges for her assistance in editing the manuscript.

Authors’ contributions

WJ, AD, and ST performed the data analysis and quality assessment. WJ, EP, JSF, SG, CL, PEH, TB, VD, NF, GR, and FD were responsible for collecting and reporting the data. WJ was the principal author. WJ, EP, JSF, CL, and PEH were the principal investigators. SG, TB, VD, AD, NF, and FD have made substantial contributions to the conception and design of the study and the interpretation of the data. WJ, EP, JSF, SG, CL, PEH, TB, VD, AD, NF, GR, ST, and FD were involved in critically reviewing the manuscript. All authors approved the final version of the manuscript.

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Authors and Affiliations

  1. Medical Oncology Department, Institut Régional du Cancer de Montpellier (ICM), 208 rue des Apothicaires, 34298, Montpellier Cedex 5, France

    William Jacot, Séverine Guiu, Véronique D’Hondt, Amélie Darlix, Nelly Firmin & Gilles Romieu

  2. Medical Oncology Department, Institut Claudius Regaud, IUCT-Oncopole, 1 avenue Irène Joliot-Curie, 31059, Toulouse, France

    Elvire Pons & Florence Dalenc

  3. Medical Oncology Department, Institut de Cancérologie de l’Ouest, Boulevard Professeur Jacques Monod, 44805, Saint-Herblain, France

    Jean-Sébastien Frenel

  4. Breast Pathology Unit, Centre François Baclesse, 3 Avenue du Général Harris, 14000, Caen, France

    Christelle Levy

  5. Medical Oncology Department, Centre Léon Bérard, 28 Prom. Léa et Napoléon Bullukian, 69008, Lyon, France

    Pierre Etienne Heudel & Thomas Bachelot

  6. Biometrics Unit, Institut régional du Cancer de Montpellier (ICM), 208 rue des Apothicaires, 34298, Montpellier, France

    Simon Thezenas

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  1. William Jacot
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Correspondence to William Jacot.

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Conflict of interest

WJ and SG are board members for Roche, PEH is a board member for Roche and EISAI, and TB is a board member for Roche, Novartis, and Astra Zeneca. WJ has received research fundings from Roche and Astra Zeneca, PEH has received research fundings from Astra Zeneca, and TB has received research fundings from Roche, Novartis, and Astra Zeneca. The other authors declare that they have no conflict of interest.

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Jacot, W., Pons, E., Frenel, JS. et al. Efficacy and safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with brain metastases. Breast Cancer Res Treat 157, 307–318 (2016). https://doi.org/10.1007/s10549-016-3828-6

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