FDA Grants T-DXd Breakthrough Therapy Designation in HR+/HER2-Low Breast Cancer

• The FDA has granted breakthrough therapy designation to fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in unresectable or metastatic hormone receptor-positive (HR+)/HER2-low or HER2-ultralow breast cancer.
• The designation is supported by data from the phase 3 DESTINY-Breast06 study (NCT04494425).
• T-DXd has received 8 breakthrough therapy designations, including 4 in metastatic breast cancer.

The antibody-drug conjugate T-DXd has been granted breakthrough therapy designation by the FDA for the treatment of patients with unresectable HR+/HER2-low or -ultralow breast cancer who have received either 2 lines of endocrine therapy in the metastatic setting or

1 line of endocrine therapy if they had demonstrated disease progression within 6 months of starting first-line treatment with endocrine therapy in combination with a CDK4/6 inhibitor or within 24 months of the start of adjuvant endocrine therapy.¹

Breakthrough therapy designation is intended to accelerate the development and regulatory review of agents that treat serious medical conditions and fill unmet needs. T-DXd has received 8 breakthrough therapy designations, including 4 in metastatic breast cancer.

“If approved, [T-DXd] could once again change the treatment paradigm for certain patients with breast cancer, pushing past old boundaries and broadening the number of people who may be eligible for a HER2- directed therapy,” said Ken Takeshita, MD, global head of research and development at Daiichi Sankyo, in a press release.

The designation is supported by data from the DESTINY-Breast06 study that were presented as a late-breaking abstract at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting earlier this year. Here, T-DXd demonstrated a median progression-free survival (PFS) in patients with HR+/HER2-low disease of 13.2 months vs 8.1 months with chemotherapy as assessed by blinded independent central review, with a 38% (HR, 0.62; 95% CI, 0.51-0.74; P <.0001) reduction in the risk of disease progression or death.²

In patients with HER2-ultralow disease, there was a 22% reduction in the risk of disease progression or death with T-DXd, with a median PFS of 13.2 months vs 8.3 months with chemotherapy (HR, 0.78; 95% CI, 0.50-1.21).

“There is a trend for positive overall survival with the landmark analysis of 1 year. Patients alive are 81% in the chemotherapy arm vs 87% in the T-DXd arm,” Giuseppe Curigliano, MD, PhD, professor of medical oncology at the University of Milan, the head of the division of early drug development at the European Institute of Oncology, and principal investigator for the trial, said in an interview with Targeted Oncology^TM.

REFERENCES:

1. ENHERTU® granted breakthrough therapy designation in U.S. for certain patients with HER2 low or HER2 ultralow metastatic breast cancer. News release. Daiichi-Sankyo. August 19, 2024. Accessed August 19, 2024. https://tinyurl.com/yuz2vdm9

2. ENHERTU® demonstrated a median progression-free survival of 13.2 months in HR positive, HER2 low and HER2 ultralow metastatic breast cancer following one or more lines of endocrine therapy. News release. Daiichi-Sankyo. June 2, 2024. Accessed August 19, 2024. https://tinyurl.com/49bf24bz