Manali Bhave, MD, an assistant professor in the Department of Hematology and Medical Oncology at Winship Cancer Institute, Emory University School of Medicine, discusses [fam-] trastuzumab deruxtecan in HER2-positive breast cancer.
Manali Bhave, MD, an assistant professor in the Department of Hematology and Medical Oncology at Winship Cancer Institute, Emory University School of Medicine, discusses the promise of [fam-] trastuzumab deruxtecan in HER2-positive breast cancer.
[Fam-] trastuzumab deruxtecan is a promising antibody-drug conjugate under investigation. It has a novel payload, which is a topoisomerase inhibitor, with 10 times the potency of irinotecan. Importantly, it has a higher drug—antibody ratio, which is approximately double that of ado-trastuzumab emtansine (T-DM1; Kadcyla). T-DM1 has a drug–antibody ratio of about 3.5, while [fam-] trastuzumab deruxtecan has a ratio of 7.8. Moreover, it is able to permeate past the membrane. As such, it has been used in trials with women who have HER2 overexpression as well as those with HER2-low breast cancers, says Bhave.
Originally, the agent showed an objective response rate (ORR) of approximately 60% and an improvement in median progression-free survival (PFS) in a heavily pretreated group of patients with metastatic disease. Accordingly, the agent was moved into the pivotal phase II DESTINY-Breast01 trial, which confirmed the ORRs and improvement in PFS.
Now, the agent is under investigation in 2 phase III trials. The first trial is underway and is comparing [fam-] trastuzumab deruxtecan with either a trastuzumab (Herceptin)-based regimen or a lapatinib (Tykerb)/capecitabine regimen in heavily pretreated women who have received trastuzumab and T-DM1. In the DESTINY-Breast03 trial, women who have progressed on a trastuzumab/taxane regimen will be randomized to [fam-] trastuzumab deruxtecan or T-DM1, says Bhave.