title: Tumour biology, metastatic sites and taxanes sensitivity as determinants of eribulin mesylate efficacy in breast cancer: results from the ERIBEX retrospective, international, multicenter study.
abstract: BACKGROUND
  Our retrospective, international study aimed at evaluating the activity and safety of eribulin mesylate (EM) in pretreated metastatic breast cancer (MBC) in a routine clinical setting.
  
  
  METHODS
  Patients treated with EM for a locally advanced or MBC between March 2011 and January 2014 were included in the study. Clinical and biological assessment of toxicity was performed at each visit. Tumour response was assessed every 3 cycles of treatment. A database was created to collect clinical, pathological and treatment data.
  
  
  RESULTS
  Two hundred and fifty-eight patients were included in the study. Median age was 59 years old. Tumours were Hormone Receptor (HR)-positive (73.3 %) HER2-positive (10.2 %), and triple negative (TN, 22.5 %). 86.4 % of the patients presented with visceral metastases, mainly in the liver (67.4 %). Median previous metastatic chemotherapies number was 4 [1-9]. Previous treatments included anthracyclines and/or taxanes (100 %) and capecitabine (90.7 %). Median number of EM cycles was 5 [1-19]. The relative dose intensity was 0.917. At the time of analysis (median follow-up of 13.9 months), 42.3 % of the patients were still alive. The objective response rate was 25.2 % (95 %CI: 20-31) with a 36.1 % clinical benefit rate (CBR). Median time to progression (TTP) and overall survival were 3.97 (95 %CI: 3.25-4.3) and 11.2 (95 %CI: 9.3-12.1) months, respectively. One- and 2-year survival rates were 45.5 and 8.5 %, respectively. In multivariate analysis, HER2 positivity (HR = 0.29), the presence of lung metastases (HR = 2.49) and primary taxanes resistance (HR = 2.36) were the only three independent CBR predictive factors, while HR positivity (HR = 0.67), the presence of lung metastases (HR = 1.52) and primary taxanes resistance (HR = 1.50) were the only three TTP independent prognostic factors. Treatment was globally well tolerated. Most common grade 3-4 toxicities were neutropenia (20.9 %), peripheral neuropathy (3.9 %), anaemia (1.6 %), liver dysfunction (0.8 %) and thrombocytopenia (0.4 %). Thirteen patients (5 %) developed febrile neutropenia.
  
  
  CONCLUSIONS
  EM is an effective new option in heavily pretreated MBC, with a favourable efficacy/safety ratio in a clinical practice setting. Our results comfort the use of this new molecule and pledge for the evaluation of EM-trastuzumab combination in this setting. Tumour biology, primary taxanes sensitivity and metastatic sites could represent useful predictive and prognostic factors.
authors.affiliation: Département de Pharmacie Clinique, Institut régional du Cancer de Montpellier (ICM), 208, rue des Apothicaires, 34298, Montpellier Cedex 5, France. Melodie.DellOva@chu-fortdefrance.fr.
authors.forename: Mélodie
authors.initials: M
authors.lastname: Dell'Ova
authors.affiliation: Medical Oncology Department, Institut Claudius Regaud, IUCT- Oncopole, Toulouse, France. DeMaio.Eleonora@iuct-oncopole.fr.
authors.forename: Eléonora
authors.initials: E
authors.lastname: De Maio
authors.affiliation: Medical Oncology Department, Centre Georges-François Leclerc, Dijon, France. sguiu@cgfl.fr.|Breast Center (CePO), University Hospital CHUV, Rue du Bugnon 46, 1011, Lausanne, Switzerland. sguiu@cgfl.fr.
authors.forename: Séverine
authors.initials: S
authors.lastname: Guiu
authors.affiliation: Département de Biostatistiques, Institut régional du Cancer de Montpellier (ICM), 208, rue des Apothicaires, 34298, Montpellier Cedex 5, France. Lise.Roca@icm.unicancer.fr.
authors.forename: Lise
authors.initials: L
authors.lastname: Roca
authors.affiliation: Medical Oncology Department, Institut Claudius Regaud, IUCT- Oncopole, Toulouse, France. dalenc.florence@iuct-oncopole.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Dalenc
authors.affiliation: Département d'Oncologie Médicale, Institut régional du Cancer de Montpellier (ICM), 208, rue des Apothicaires, 34298, Montpellier Cedex 5, France. Anna.DurigovaAbdouh@hcuge.ch.|Medical Oncology Department, University Hospital of Geneva, Gabrielle-Perret-Gentil 4, 1211, Geneva, Switzerland. Anna.DurigovaAbdouh@hcuge.ch.
authors.forename: Anna
authors.initials: A
authors.lastname: Durigova
authors.affiliation: Département de Pharmacie Clinique, Institut régional du Cancer de Montpellier (ICM), 208, rue des Apothicaires, 34298, Montpellier Cedex 5, France. Frederic.Pinguet@icm.unicancer.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pinguet
authors.affiliation: Département de Pharmacie Clinique, Institut régional du Cancer de Montpellier (ICM), 208, rue des Apothicaires, 34298, Montpellier Cedex 5, France. khedidja.Bekhtari@icm.unicancer.fr.
authors.forename: Khedidja
authors.initials: K
authors.lastname: Bekhtari
authors.affiliation: Département d'Oncologie Médicale, 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: Département d'Oncologie Médicale, Institut régional du Cancer de Montpellier (ICM), 208, rue des Apothicaires, 34298, Montpellier Cedex 5, France. stephane.pouderoux@icm.unicancer.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pouderoux
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D019008:Drug Resistance, Neoplasm; D005260:Female; D005663:Furans / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007659:Ketones / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D043823:Taxoids / Q000494:pharmacology*; D016896:Treatment Outcome; D055815:Young Adult; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005663:Furans; D007659:Ketones; D043823:Taxoids; C490954:eribulin; D000095662:Polyether Polyketides