by Dr. C.H. Weaver M.D. updated 7/2019
Following the U.S. Food and Drug Administration (FDA) Breakthrough Therapy designation for DS-8201 (trastuzumab deruxtecan) a Lancet Oncology publications of the Phase I dose-expansion results in HER2-positive metastatic breast was reported in May 2019. DS-8201 is an investigational HER2-targeting antibody drug conjugate (ADC), for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with Herceptin and Perjeta and have disease progression after ado-trastuzumab (T-DM1).(1)
About DS-8201 (trastuzumab deruxtecan)
ADCs are a type of targeted cancer medicine that deliver cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. DS-8201 is a smart chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor (DXd) payload by a tetrapeptide linker. It is designed to deliver enhanced cell destruction upon release inside the cell and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.
About HER2-Positive Breast Cancer
About one in five patients with breast cancer over-express HER2 (make too much of), a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells, which is associated with aggressive disease.(2) Many tumors advance to the point where no currently approved HER2-targeting treatment continues to control the disease. Furthermore, there is no standard of care for HER2-positive tumors following treatment with Herceptin, Perjeta and T-DM1.(3)
The results of the breast cancer trial reported that an objective response rate of 60% and a disease control rate of 94% was attained at the recommended expansion dose of 5.4 or 6.4 mg/kg of DS-8201.(4) An average 20.7 months median duration of response in HER2-positive metastatic breast cancer patients previously treated with trastuzumab emtansine was achieved. Patients enrolled in this part of the trial had a median of seven prior lines of treatment, including trastuzumab and trastuzumab emtansine, and in 86% of cases, pertuzumab.
Breakthrough Therapy designation is designed to expedite the development and review of medicines that may demonstrate substantial benefit over currently available treatments in order to ensure that patients with serious diseases have access to new treatments as soon as possible. Currently, there is no FDA-approved therapy for patients with HER2-positive metastatic breast cancer with disease progression following treatment with other HER2-targeting agents Herceptin, Perjeta and T-DM1.
- Doi T, et al. J Clin Oncol. 2017;35(15):108
- American Cancer Society. Breast Cancer Overview. 2016.
- NCCN Guidelines. Breast Cancer. Version 2.2017.