NE Oncology Issue – May 2014
The decision of which treatment strategy to use for patients with breast cancer is based on multiple factors, including tumour surface markers and clinical factors. Molecular techniques, including gene expression profiling, have helped to refine the classification of breast cancer, and to assess response to therapy and prognosis.1 One molecular determinant of therapy is whether or not the tumour is human epidermal growth factor receptor 2-positive (HER2+).2 A number of HER2-targeted therapies have been developed for patients with HER2+ tumours, including monoclonal antibodies (e.g., trastuzumab and pertuzumab), the monoclonal antibody-drug conjugate trastuzumab emtansine, and tyrosine kinase inhibitors (e.g., lapatinib and afatinib).
For patients with recurrent or metastatic breast cancer that is hormone receptor-positive (HR+), antiestrogen first-line treatment regimens, including the steroidal aromatase inhibitor exemestane, have shown significant disease control with better-tolerated toxicity than standard chemotherapy.3
The latest results from clinical trials investigating treatment for HER2+, and HR+/HER2-negative (HER2–) breast cancer, as well as a cost analysis of treatment, were presented at the 2013 San Antonio Breast Cancer Symposium (SABCS).
- The dual HER2 blockade of lapatinib plus trastuzumab appears to provide superior benefit (i.e., pathological complete response, event-free survival, and overall survival) than either agent alone in patients with HER2+/ HR-negative tumours.
- The combination of pertuzumab, trastuzumab, and vinorelbine as first-line treatment of HER2+ locally advanced or metastatic breast cancer showed an acceptable safety profile with no new safety signals observed.
- The combination of everolimus plus exemestane in the BOLERO-2 trial significantly improved the overall response rate compared with placebo plus exemestane in patients with HR+, HER2– advanced breast cancer who had progressed during or after nonsteroidal aromatase inhibitor therapy.
- The benefit-risk profile of the combination of pertuzumab, trastuzumab, and docetaxel supports this regimen as the preferred therapy for patients with HER2+, first-line metastatic breast cancer from Asia and all other geographic regions.
- In a phase II trial, the combination of eribulin plus trastuzumab as first-line therapy for locally recurrent or metastatic HER2+ breast cancer resulted in an objective response rate of 71.2%, a median progression-free survival of 11.6 months, and an acceptable safety profile.
- A cost analysis of managing treatment-related adverse events from the perspective of Canadian public payers demonstrated that using trastuzumab emtansine for the treatment of HER2+ breast cancer resulted in considerable cost savings due to the improved safety profile compared with capecitabine plus lapatinib and trastuzumab plus docetaxel.
- The combination of afatinib (40 mg/day) plus vinorelbine (25 mg/m2/week) showed early signs of clinical activity in Japanese patients with confirmed refractory advanced/metastatic solid tumours.
References: 1. Schnitt SJ. Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy. Modern Pathology 2010;23:S60–4. 2. Li SG and Li L. Targeted therapy in HER2-positive breast cancer (review). Biomedical Reports 2013;1:499–505. 3. Glück S. Exemestane as first-line therapy in postmenopausal women with recurrent or metastatic breast cancer. Am J Clin Oncol 2010;33:314–9.
Carolyn Owen, MD
Dr. Carolyn Owen completed postgraduate training in internal medicine and hematology at the University of Ottawa and the University of British Columbia, respectively, followed by a research fellowship in molecular genetics at Barts and the London School of Medicine and Dentistry in London, UK. Her research focused on familial myelodysplasia and acute myeloid leukemia. She is currently an Assistant Professor at the Foothills Medical Centre & Tom Baker Cancer Centre, and her clinical interests are low-grade lymphoma and chronic lymphocytic leukemia. She is also the local principal investigator in Calgary for several clinical trials in these areas.
Douglas A. Stewart, BMSc, MD, FRCPC
Dr. Douglas A. Stewart is currently a professor in the Departments of Oncology and Medicine, and Chief of the Division of Hematology and Hematological Malignancies at the University of Calgary. Since July 1994, he has been practising medical oncology at the Tom Baker Cancer Centre in Calgary, where he is a member of the Breast Cancer and Hematology Tumour Groups, Leader of the Hematology/Blood and Marrow Transplant Program, and Provincial Leader of the Hematology Tumour Team for the Alberta Health Services Cancer Care Program. His research interests focus on clinical trials involving hematological malignancies and hematopoietic stem cell transplantation. Dr. Stewart has authored over 80 peer-reviewed manuscripts and over 120 abstracts.
Richard R. Furman, MD
Dr. Furman is a member of the Lymphoma/Myeloma Service in the Division of Hematology/ Oncology at the New York Weill Cornell Medical Center. He is head of the chronic lymphocytic leukemia (CLL) and Waldenstrom’s macroglobulinemia (WM) program at Weill Medical College, and focuses on identifying new and promising therapies for patients with CLL and WM. Along with collaborators at Columbia Presbyterian, Johns Hopkins, Roswell Park Cancer Institute, and Ohio State University, Dr. Furman has initiated the Waldenstrom’s Research Consortium in order to enhance treatment and understanding of WM.