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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.

Javier Cortés 1 Pierre Fumoleau 2 Giulia Valeria Bianchi 3 Teresa Petrella 4 Karen Gelmon 5 Xavier Pivot 6 Shailendra Verma 7 Joan Albanell 8 Pierfranco Conte 9 Ana Lluch 10 Stefania Salvagni 11 Véronique Servent 12 Luca Gianni 13 Maurizio Scaltriti 14 Graham Ross 15 Joanna Dixon 15 Tania Szado 15 José Baselga 14
1 Joan Albanell, Hospital del Mar
2 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
3 Fundazione IRCCS Istituto Nazionale Dei Tumori
4 Odette Cancer Center
5 British Columbia Cancer Agency
6 Service d'oncologie Médicale
7 Ottawa Regional Cancer Centre
8 Medical Oncology Department, Breast Cancer Unit. Molecular Therapeutics and Biomarkers in Breast Cancer, Cancer Research Program
9 University hospital Modena
10 Hospital Clinico
11 Ospedale Regionale
12 UNICANCER/Lille - Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille]
13 IRCCS Istituto Nazionale dei Tumori [Milano]
14 Massachusetts General Hospital Cancer Center
15 Roche Products
Abstract : PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.
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https://www.hal.inserm.fr/inserm-00821137
Contributor : Philippe Saas <>
Submitted on : Tuesday, May 7, 2013 - 3:52:30 PM
Last modification on : Wednesday, June 10, 2020 - 6:18:18 PM

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Javier Cortés, Pierre Fumoleau, Giulia Valeria Bianchi, Teresa Petrella, Karen Gelmon, et al.. 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.. Journal of Clinical Oncology, American Society of Clinical Oncology, 2012, 30 (14), pp.1594-600. ⟨10.1200/JCO.2011.37.4207⟩. ⟨inserm-00821137⟩

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