NE Oncology Issue – May 2014
Piwko C, et al. SABCS 2013:P4-12-16
Trastuzumab emtansine, approved in Canada on September 11, 2013, is an antibody-drug conjugate whose efficacy and safety have been reported previously in the EMILIA1 and TDM4450g2 studies. Trastuzumab emtansine, as a single agent, is indicated for the treatment of patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) who have received both prior treatment with trastuzumab and a taxane, separately or in combination. Patients should have either received prior therapy for metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy.
The objective of this study was to estimate and compare the costs of managing treatment-related adverse events (AEs) of trastuzumab emtansine, capecitabine plus lapatinib, and trastuzumab plus docetaxel, as reported in the EMILIA and TDM4450g trials, from the perspective of Canadian public payers.3
- This analysis considered treatment-related grade ≥3 AEs as well as grade 2 AEs that occurred in ≥5% of patients in either arm of either study. (Table 1)
- To identify studies reporting on the Canadian costs associated with managing the relevant treatment- related AEs, two researchers independently conducted literature searches on the Medline and Embase databases.
- Missing costing information from the literature was complemented by a survey with Canadian clinical experts. If experts were unable to report a cost for an AE, the cost was assumed to be $0.
- An Excel-based spreadsheet model was utilized to calculate the average cost, reported in 2012 Canadian dollars (CAD), of managing the treatment-related AEs.
- Based on clinical expert opinion, management of grade 2 AEs was assumed to cost the same as grade ≥3 AEs.
- For the sensitivity analysis, management of grade 2 AEs was assumed to cost only 50% of grade ≥3 AEs.
- The number of occurrences of each AE was obtained from the two trials for each treatment arm.
- Unit costs for resources were obtained from standard Canadian costing sources, such as the Ontario Drug Benefit Formulary.
- The number of occurrences of each AE was multiplied by the average cost per occurrence to calculate the total cost of each AE. All costs were summed to calculate the total cost of all AEs for each treatment arm. The calculated total costs of all AEs were divided by the number of patients in each arm to calculate the cost of AEs per patient in each arm.
- Study limitations included:
- Costs were assigned for each AE, despite the fact that in the trials, the AEs could have been managed by dose reductions alone;
- Less than half of the included references stated the degree of severity of the AEs that were costed (was tested in sensitivity analyses).
- Due to the different regimens studied, the results from the EMILIA and TDM4450g trials were not directly comparable and were, therefore, analyzed separately.
- The average costs of treatment-related grade 2 and grade ≥3 AEs that occurred in either arm of the EMILIA and TDM4450g studies are shown in Table 2.
- In the EMILIA trial, the management of treatmentrelated AEs resulted in higher per patient average costs for capecitabine plus lapatinib of $6,780 compared with $1,919 for trastuzumab emtansine. This resulted in a cost difference per patient of $4,861. (Figure 1)
- In the TDM4450g trial, the management of treatment- related AEs resulted in higher per patient average costs for trastuzumab plus docetaxel of $16,370 compared with $1,507 for trastuzumab emtansine. This resulted in an average cost difference of $14,864. (Figure 1)
- The results of the sensitivity analysis showed:
- In the EMILIA trial, the management of treatment-related AEs would result in higher per patient costs for capecitabine plus lapatinib of $2,776 ($723–$4,829), when compared with trastuzumab emtansine.
- In the TDM4450g trial, the management of treatmentrelated AEs would result in higher per patient costs for trastuzumab plus docetaxel of $14,219 ($4,008–$24,271), when compared with trastuzumab emtansine.
- The results were robust in various sensitivity analyses (results to be presented in future publications).
- The main cost drivers in this analysis were the management of treatment-related neutropenia, thrombocytopenia, vomiting, and diarrhea. These AEs are costly as they may require hospital admissions, emergency room and doctor visits, intravenous fluids, expensive medications, medical procedures, and increased caregiver time.
- This analysis demonstrated that utilizing trastuzumab emtansine for the management of HER2+ breast cancer results in considerable cost savings of treatment-related AE management due to the improved safety profile compared with capecitabine plus lapatinib and with trastuzumab plus docetaxel.
Reference: 1. Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012;367:1783–91. 2. Hurvitz SA, Dirix L, Kocsis J, et al. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol 2013;31:1157–63. 3. Piwko C, Moser A, Le P, et al. Safety profile and costs of related adverse events of trastuzumab emtansine compared to other regimens in the Canadian health care system. SABCS Abstracts 2013:P4-12-16.
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.