title: Pertuzumab monotherapy after trastuzumab-based treatment and subsequent reintroduction of trastuzumab: activity and tolerability in patients with advanced human epidermal growth factor receptor 2-positive breast cancer.
abstract: OBJECTIVE
  The combination of pertuzumab and trastuzumab resulted in a clinical benefit rate (CBR) of 50% in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer whose disease progressed during prior trastuzumab-based therapy. To define whether this previously observed encouraging activity was a result of the combination of pertuzumab and trastuzumab or of pertuzumab alone, we recruited a third cohort of patients who received pertuzumab without trastuzumab. We then investigated the impact of reintroducing trastuzumab to patients whose disease progressed on pertuzumab monotherapy.
  
  
  METHODS
  Twenty-nine patients with HER2-positive breast cancer whose disease progressed during prior trastuzumab-based therapy received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks) until progressive disease or unacceptable toxicity. Seventeen patients with disease progression continued to receive pertuzumab (at the same dose), with the addition of trastuzumab (4 mg/kg loading dose and then 2 mg/kg weekly or 8 mg/kg loading dose and then 6 mg/kg every 3 weeks).
  
  
  RESULTS
  All 29 patients enrolled for pertuzumab monotherapy experienced disease progression. The objective response rate (ORR) and CBR were 3.4% and 10.3%, respectively, during pertuzumab monotherapy. With the addition of trastuzumab, the ORR and CBR were 17.6% and 41.2%, respectively. Progression-free survival was longer with combination therapy than pertuzumab monotherapy (17.4 v 7.1 weeks, respectively). Treatment was well tolerated with minimal cardiac dysfunction.
  
  
  CONCLUSIONS
  Although pertuzumab has some activity in patients with HER2-positive breast cancer that progressed during therapy with trastuzumab, the combination of pertuzumab and trastuzumab seems to be more active than monotherapy.
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Cortés
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.forename: Giulia Valeria
authors.initials: GV
authors.lastname: Bianchi
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Petrella
authors.forename: Karen
authors.initials: K
authors.lastname: Gelmon
authors.forename: Xavier
authors.initials: X
authors.lastname: Pivot
authors.forename: Shailendra
authors.initials: S
authors.lastname: Verma
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.forename: Pierfranco
authors.initials: P
authors.lastname: Conte
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Stefania
authors.initials: S
authors.lastname: Salvagni
authors.forename: Veronique
authors.initials: V
authors.lastname: Servent
authors.forename: Luca
authors.initials: L
authors.lastname: Gianni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Scaltriti
authors.forename: Graham A
authors.initials: GA
authors.lastname: Ross
authors.forename: Joanna
authors.initials: J
authors.lastname: Dixon
authors.forename: Tania
authors.initials: T
authors.lastname: Szado
authors.forename: José
authors.initials: J
authors.lastname: Baselga
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D018579:Patient Selection; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D018570:Risk Assessment; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C485206:pertuzumab