title: Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy.
abstract: PURPOSE; Pertuzumab, a human epidermal growth factor receptor 2 (HER2) -targeted monoclonal antibody, potently inhibits HER2 dimerization and HER-mediated signaling pathways. Pertuzumab and the approved HER2-targeted monoclonal antibody trastuzumab have complementary mechanisms of action and result in enhanced antitumor activity when combined. This phase II trial assessed the efficacy and safety profile of the combination in patients with HER2-positive breast cancer whose disease had progressed during prior trastuzumab-based therapy.
  
  
  METHODS
  This was a multicenter, open-label, single-arm, Simon two-stage study. Patients with advanced HER2-positive breast cancer in whom disease progression had occurred during prior trastuzumab-based therapy received trastuzumab weekly (4 mg/kg loading dose, then 2 mg/kg every week) or every 3 weeks (8 mg/kg loading dose, then 6 mg/kg every 3 weeks) and pertuzumab every 3 weeks (840 mg loading dose, then 420 mg every 3 weeks). Treatment continued until disease progression or excessive toxicity.
  
  
  RESULTS
  All 66 patients were assessable for efficacy and safety. The objective response rate was 24.2%, and the clinical benefit rate was 50%. Five patients (7.6%) experienced a complete response, 11 patients (16.7%) experienced a partial response, and 17 patients (25.8%) experienced stable disease of > or = 6 months. Median progression-free survival was 5.5 months. Overall, the combination of pertuzumab and trastuzumab was well tolerated, and adverse events were mild to moderate. Cardiac dysfunction was minimal, and no patients withdrew as a result of cardiac-related adverse events.
  
  
  CONCLUSIONS
  The combination of pertuzumab and trastuzumab is active and well tolerated in patients with metastatic HER2-positive breast cancer who had experienced progression during prior trastuzumab therapy.
authors.affiliation: Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Paseo Vall d'Hebron 119-129, Barcelona, Spain E-08035. jbaselga@vhebron.net
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Karen A
authors.initials: KA
authors.lastname: Gelmon
authors.forename: Shailendra
authors.initials: S
authors.lastname: Verma
authors.forename: Andrew
authors.initials: A
authors.lastname: Wardley
authors.forename: Pierfranco
authors.initials: P
authors.lastname: Conte
authors.forename: David
authors.initials: D
authors.lastname: Miles
authors.forename: Giulia
authors.initials: G
authors.lastname: Bianchi
authors.forename: Javier
authors.initials: J
authors.lastname: Cortes
authors.forename: Virginia A
authors.initials: VA
authors.lastname: McNally
authors.forename: Graham A
authors.initials: GA
authors.lastname: Ross
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.forename: Luca
authors.initials: L
authors.lastname: Gianni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D013318:Stroke Volume / Q000187:drug effects; D000068878:Trastuzumab; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab