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

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 encourag...

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Vydáno v:Journal of clinical oncology Ročník 30; číslo 14; s. 1594
Hlavní autoři: Cortés, Javier, Fumoleau, Pierre, Bianchi, Giulia Valeria, Petrella, Teresa M, Gelmon, Karen, Pivot, Xavier, Verma, Shailendra, Albanell, Joan, Conte, Pierfranco, Lluch, Ana, Salvagni, Stefania, Servent, Veronique, Gianni, Luca, Scaltriti, Maurizio, Ross, Graham A, Dixon, Joanna, Szado, Tania, Baselga, José
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 10.05.2012
Témata:
Adult
Age Factors
Aged
Antibodies, Monoclonal, Humanized - administration & dosage
Antibodies, Monoclonal, Humanized - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Breast Neoplasms - drug therapy
Breast Neoplasms - metabolism
Breast Neoplasms - mortality
Breast Neoplasms - pathology
Disease Progression
Disease-Free Survival
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Humans
Maximum Tolerated Dose
Middle Aged
Neoplasm Invasiveness - pathology
Neoplasm Staging
Patient Selection
Prognosis
Prospective Studies
Receptor, ErbB-2 - metabolism
Risk Assessment
Survival Analysis
Trastuzumab
Treatment Outcome
ISSN:1527-7755, 1527-7755
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Shrnutí: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. 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). 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. 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.
Bibliografie:ObjectType-Article-2
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1527-7755
1527-7755
DOI:10.1200/JCO.2011.37.4207