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

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.

• Authors: Javier Cortés, Pierre Fumoleau, Giulia Valeria Bianchi, Teresa M Petrella, Karen Gelmon, Xavier Pivot, Shailendra Verma, Joan Albanell, Pierfranco Conte, Ana Lluch, Stefania Salvagni, Veronique Servent, Luca Gianni, Maurizio Scaltriti, Graham A Ross, Joanna Dixon, Tania Szado, José Baselga
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 30 Issue 14 Pg. 1594-600 (May 10 2012) ISSN: 1527-7755 [Electronic] United States
• PMID: 22393084 (Publication Type: Comparative Study, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Receptor, ErbB-2
• pertuzumab
• Trastuzumab

Topics

• Adult
• Age Factors
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, metabolism, mortality, 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