title: A phase I/II trial of the safety and clinical activity of a HER2-protein based immunotherapeutic for treating women with HER2-positive metastatic breast cancer.
abstract: The objectives of this phase I/II study (NCT00140738) were to evaluate the safety and clinical activity of a cancer immunotherapeutic agent (recombinant HER2 protein (dHER2) and the immunostimulant AS15) in patients with HER2-overexpressing metastatic breast cancer (MBC). Forty HER2-positive MBC patients received up to 18 doses (12q2w, 6q3w) of dHER2 immunotherapeutic, as first- or second-line therapy following response to trastuzumab-based treatment as maintenance. Toxicity was graded by the Common Terminology Criteria for Adverse Events (CTCAE) and clinical activity was evaluated by target lesion assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST). Immunogenicity was assessed. The dHER2 immunotherapeutic was well tolerated: grade 1/2 adverse events (AEs) were most common. No cardiac events were observed and one patient experienced an asymptomatic decrease of left ventricular ejection fraction below the normal range (47 %). Both humoral and cellular immunogenicity to the dHER2 antigen was observed. No patient discontinued the immunizations because of AEs but 35/40 withdrew prematurely, 34 because of disease progression (24/34 before or at the tumor assessment after dose 6). One patient achieved a complete response lasting 11 months and one patient had a partial response lasting 3.5 months. Ten patients experienced stable disease ≥26 weeks with 4/10 still in stable disease at the last tumor assessment after 47 weeks. Immunization of MBC patients with the dHER2 immunotherapeutic was associated with minimal toxicity and no cardiac events. Clinical activity was observed with two objective responses and prolonged stable disease for 10/40 patients.
authors.affiliation: Early Drug Development for Innovative Therapies Division, Istituto Europeo di Oncologica di Milano, Via Ripamonti, 435, 20141, Milan, Italy. giuseppe.curigliano@ieo.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
authors.affiliation: Institut régional du Cancer de Montpellier, Montpellier, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
authors.affiliation: Institut de Cancérologie de l'Ouest, Nantes, France.
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Dorval
authors.affiliation: Department of Medical Oncology, Clinique Saint-Pierre, Ottignies, Belgium.
authors.forename: Lionel
authors.initials: L
authors.lastname: Duck
authors.affiliation: Oncology-Hematology Department, Grand Hopital de Charleroi, Charleroi, Belgium.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Canon
authors.affiliation: Centre d'Oncologie de Gentilly, Nancy, France.
authors.forename: Celia
authors.initials: C
authors.lastname: Roemer-Becuwe
authors.affiliation: Medical Oncology Unit, 'Tor Vergata' University Hospital, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Roselli
authors.affiliation: Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
authors.forename: Silvia
authors.initials: S
authors.lastname: Neciosup
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Wivine
authors.initials: W
authors.lastname: Burny
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Andrea
authors.initials: A
authors.lastname: Callegaro
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Pedro Miguel
authors.initials: PM
authors.lastname: de Sousa Alves
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Jamila
authors.initials: J
authors.lastname: Louahed
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Brichard
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Frédéric F
authors.initials: FF
authors.lastname: Lehmann
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000378:metabolism / Q000628:therapy*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D000068878:Trastuzumab / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Breast cancer; Cancer immunotherapeutic; HER2 antigen; Vaccine