5/10/2023 0 Comments T dm1 mechanism of action![]() ![]() In February 2013, the US Food and Drug Administration (FDA) granted accelerated approval for ado-trastuzumab emtansine (Kadcyla Genentech, Inc), also known as T-DM1, for the treatment of patients with HER2-positive metastatic breast cancer who were previously treated with trastuzumab and with taxanes. 10įDA Approval of Ado-Trastuzumab Emtansine Fills an Unmet Need 9 Therapy alternatives include the combination of pertuzumab, trastuzumab, and a taxane lapatinib plus trastuzumab lapatinib plus capecitabine and the continued use of trastuzumab plus chemotherapy. 8Ĭurrently, treatment strategies for patients with trastuzumab-resistant HER2-positive breast cancer are selected on the basis of patient-specific factors (ie, age, comorbidities), disease- related factors, and cost. 7 Concerted efforts are under way to identify the mechanisms of trastuzumab resistance, as well as novel “druggable” targets for this patient population. In 2013, approximately 13,000 patients with HER2-positive metastatic breast cancer will have disease recurrence after trastuzumab treatment. However, primary and secondary resistance to trastuzumab occurs in the advanced breast cancer setting: none of these patients is cured. 4 In addition, 2 meta-analyses have confirmed the OS benefit of adding HER2-targeted therapy to standard treatment in patients with early-stage or metastatic HER2-positive breast cancer. 3 The first phase 3 clinical trial that compared trastuzumab plus chemotherapy versus chemotherapy alone in patients with HER2-positive metastatic breast cancer demonstrated robust improvements in response rate (50% vs 32%, respectively), median time to progression (7.4 months vs 4.6 months, respectively), and median overall survival ( 25.1 months vs 20.3 months, respectively) with the addition of trastuzumab. Much of the increased survival for patients with HER2-positive breast cancer is attributed to the development of HER2-targeted therapies, including trastuzumab (Herceptin), pertuzumab (Perjeta), and lapatinib (Tykerb). 2 Since 1989, death rates from breast cancer have declined, with relatively larger decreases in women aged <50 years, in part as a result of earlier detection and increasingly improved treatments. The American Cancer Society estimates that approximately 232,340 women will be diagnosed with invasive breast cancer, and approximately 39,620 deaths will occur from the disease in 2013. Unmet Need in Trastuzumab-Resistant Breast Cancer This protein is a cell-surface receptor that compels the tumor cell to grow and to divide more frequently than normal, making HER2-positive breast cancer an aggressive phenotype.īefore the advent of HER2-directed therapies, patients diagnosed with HER2-positive disease had significantly shorter disease-free survival compared with patients with other breast cancer subtypes. The HER2 gene, which resides on chromosome 17, directs tumor cells to manufacture HER2 protein. Approximately 25% of women who are diagnosed with breast cancer have HER2-positive tumors.
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