Dr Mina on the Evolution of T-DM1 and T-DXd in HER2+ Breast Cancer

Lida A. Mina, MD, senior associate consultant, Women’s Cancer Program, chair, Mayo Arizona Breast Cancer working group, GYN disease working group, Division of Hematology and Medical Oncology, Mayo Clinic Comprehensive Cancer Center, discusses the evolution of the antibody-drug conjugates (ADCs) fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) and ado-trastuzumab emtansine (Kadcyla; T-DM1) in HER2-positive breast cancer.

Both T-DXd and T-DM1 have shown benefit across clinical trials in HER2-positive breast cancer and are approved for the treatment of patient’s within this space, Mina begins. Single-agent T-DM1 previously gained approval in February of 2013 for the treatment of patients with HER2-positive metastatic breast cancer who have previously progressed on trastuzumab (Herceptin) and a taxane either separately or in combination, Mina states.

In December 2019, T-DXd was added to the armamentarium after receiving an accelerated approval in patients with unresectable or metastatic HER2-positive breast cancer who were previously treated with an anti-HER2-based regimen either in the metastatic, neoadjuvant, or adjuvant setting and developed disease recurrence during or within 6 months of completing therapy, Mina continues. Additionally, this approval was based on findings from the phase 3 DESTINY Breast-01 trial (NCT03248492).

Data from the confirmatory phase 3 DESTINY Breast-03 trial (NCT03529110) supported the regular approval of second-line T-DXd in May 2022, Mina says. This trial directly compared the use of T-DM1 and T-DXd, showing that T-DXd improved progression-free survival (PFS) and overall survival (OS) in this population, she reports. The median PFS was 28.8 months for patients receiving T-DXd vs 6.8 months with T-DM1. The median OS was not reached with either agent, but was prolonged in the T-DXd arm. Finally, overall response rates recorded were 79.7% vs 34.2% in the T-DXd and T-DM1 arms, respectively.

These paradigm-shifting findings solidified T-DXd as the new standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer, Mina concludes.