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combined herceptin+pertuzumab therapy better than pertuzumab alone after resistance
develops to herceptin
One of the authors is Mauricio Scaltriti, who did the original preclinical work on the supersynergism between herceptin and lapatinib
J Clin Oncol. 2012 Mar 5. [Epub ahead of print]
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.
Cortés J, Fumoleau P, Bianchi GV, Petrella TM, Gelmon K, Pivot X, Verma S, Albanell J, Conte P, Lluch A, Salvagni S, Servent V, Gianni L, Scaltriti M, Ross GA, Dixon J, Szado T, Baselga J.
Source
Javier Cortés, Vall d'Hebron University Hospital; Joan Albanell, Hospital del Mar, Barcelona; Ana Lluch, Hospital Clinico Universitario, Valencia, Spain; Pierre Fumoleau, Centre Georges-François Leclerc, Dijon; Xavier Pivot, Centre Hospitalier Universitaire Jean Minjoz, Besançon; Veronique Servent, Centre Oscar Lambret, Lille, France; Giulia Valeria Bianchi, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori; Luca Gianni, Istituto Nazionale, Milan; Pierfranco Conte, University Hospital, Modena; Stefania Salvagni, Ospedale Regionale, Parma, Italy; Teresa M. Petrella, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto; Shailendra Verma, Ottawa Regional Cancer Centre, Ottawa, Ontario; Karen Gelmon, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Graham A. Ross, Joanna Dixon, and Tania Szado, Roche Products, Welwyn Garden City, United Kingdom; and Maurizio Scaltriti and José Baselga, Massachusetts General Hospital Cancer Center, Boston, MA.
Abstract
PURPOSEThe 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. PATIENTS AND METHODSTwenty-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).ResultsAll 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. CONCLUSIONAlthough 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.
PMID: 22393084
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