Dr Krill-Jackson on the Practice-Changing Effect of T-DXd in HER2+ Breast Cancer

Elisa Krill-Jackson, MD, breast oncologist, associate director of community outreach for women's health, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the impact of treatment with fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in metastatic, HER2-positive breast cancer, highlighting remaining questions with the use of trastuzumab emtansine (Kadcyla; T-DM1) in this patient population.

On May 4, 2022, the FDA granted regular approval to T-DXd for adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received an anti-HER2–based regimen in the metastatic, neoadjuvant, adjuvant setting and experienced disease recurrence during treatment or within 6 months of completing therapy.

The approval of T-DXd has greatly impacted the management of HER2-positive breast cancer, Krill-Jackson begins. This novel drug has shown superior efficacy in the second-line setting vstreatment with TDM-1, she reports. Patients treated with this agent also experience prolonged survival and improved quality of life, Krill-Jackson details. Moreover, T-DXd has demonstrated activity in a subset of patients who present with brain metastases, Krill-Jackson adds, noting that this is a historically difficult-to-treat patient population. Accordingly, T-DXd's has replaced TDM-1 as the new standard-of-care second-line therapy for patients with HER2-positive breast cancer, Krill-Jackson states.

In light of this shift in treatment, the role of T-DM1 within the HER2-positive breast cancer treatment paradigm has become less clear, Krill-Jackson continues. The emergence of effective alternative therapies, such as the phase 2 HER2CLIMB (NCT02614794) regimen of tucatinib (Tukysa), trastuzumab (Herceptin), and capecitabine (Xeloda), has further complicated decision-making with the use of TDM-1, Krill-Jackson says.

Results from the HER2CLIMB trial demonstrated the combination regimens potential to enhance survival outcomes compared with whole brain radiation therapy for individuals with treated and stable brain metastases or active brain metastases. Additionally, the benefit of using TDM-1 in patients who progressed on T-DXd has yet to be determined, especially considering the availability of newer agents, Krill-Jackson notes.

Currently, TDM-1 remains an additional option for patients in the fourth-line and beyond, but its efficacy in this context is unclear. Clinicians await further evidence from clinical trials that could elucidate the optimal role for TDM-1 in this evolving treatment landscape, Krill-Jackson concludes.