title: Efficacy and safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with brain metastases.
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.
authors.affiliation: Medical Oncology Department, Institut Régional du Cancer de Montpellier (ICM), 208 rue des Apothicaires, 34298, Montpellier Cedex 5, France. william.jacot@icm.unicancer.fr.
authors.forename: William
authors.initials: W
authors.lastname: Jacot
authors.affiliation: Medical Oncology Department, Institut Claudius Regaud, IUCT-Oncopole, 1 avenue Irène Joliot-Curie, 31059, Toulouse, France.
authors.forename: Elvire
authors.initials: E
authors.lastname: Pons
authors.affiliation: Medical Oncology Department, Institut de Cancérologie de l'Ouest, Boulevard Professeur Jacques Monod, 44805, Saint-Herblain, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Frenel
authors.affiliation: Medical Oncology Department, Institut Régional du Cancer de Montpellier (ICM), 208 rue des Apothicaires, 34298, Montpellier Cedex 5, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Guiu
authors.affiliation: Breast Pathology Unit, Centre François Baclesse, 3 Avenue du Général Harris, 14000, Caen, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Levy
authors.affiliation: Medical Oncology Department, Centre Léon Bérard, 28 Prom. Léa et Napoléon Bullukian, 69008, Lyon, France.
authors.forename: Pierre Etienne
authors.initials: PE
authors.lastname: Heudel
authors.affiliation: Medical Oncology Department, Centre Léon Bérard, 28 Prom. Léa et Napoléon Bullukian, 69008, Lyon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.affiliation: Medical Oncology Department, Institut Régional du Cancer de Montpellier (ICM), 208 rue des Apothicaires, 34298, Montpellier Cedex 5, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: D'Hondt
authors.affiliation: Medical Oncology Department, Institut Régional du Cancer de Montpellier (ICM), 208 rue des Apothicaires, 34298, Montpellier Cedex 5, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Darlix
authors.affiliation: Medical Oncology Department, Institut Régional du Cancer de Montpellier (ICM), 208 rue des Apothicaires, 34298, Montpellier Cedex 5, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Firmin
authors.affiliation: Medical Oncology Department, Institut Régional du Cancer de Montpellier (ICM), 208 rue des Apothicaires, 34298, Montpellier Cedex 5, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
authors.affiliation: Biometrics Unit, Institut régional du Cancer de Montpellier (ICM), 208 rue des Apothicaires, 34298, Montpellier, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Thezenas
authors.affiliation: Medical Oncology Department, Institut Claudius Regaud, IUCT-Oncopole, 1 avenue Irène Joliot-Curie, 31059, Toulouse, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Dalenc
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000328:Adult; D000368:Aged; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008453:Maytansine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D000068878:Trastuzumab / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D000074322:Antineoplastic Agents, Immunological; D008453:Maytansine; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Brain metastases; Breast cancer; Efficacy; HER2; T-DM1; Toxicity