ENHERTU® Receives Breakthrough Therapy Designation for HER2 Metastatic Breast Cancer
ENHERTU® has been awarded Breakthrough Therapy Designation (BTD). This designation is for the treatment of patients with unresectable or metastatic hormone receptor-positive HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC >0 <1+) breast cancer.
Who have already undergone either two lines of endocrine therapy in the metastatic setting or one line of endocrine therapy if they experienced disease progression within six months of beginning first-line treatment combined with a CDK4/6 inhibitor, or within 24 months of starting adjuvant endocrine therapy. This BTD is aimed at treating serious conditions with significant unmet medical needs.
DESTINY-Breast06 is a global, randomised, open-label, phase 3 trial assessing the safety and effectiveness of ENHERTU (5.4 mg/kg) compared to the investigator's choice of chemotherapy (capecitabine, paclitaxel, or nab-paclitaxel) in patients with HR-positive, HER2 low or HER2 ultralow advanced or metastatic breast cancer.
The primary endpoint of the trial is progression-free survival (PFS) in the HR-positive, HER2 low patient group, as measured by blinded independent central review (BICR). Key secondary endpoints include PFS across the overall trial population, overall survival (OS) in the HER2 low group, and OS in the total trial population. Other secondary endpoints involve objective response rate, duration of response, and safety. Analysis of the HER2 ultralow subgroup was not powered for statistical significance.
HER2 is a protein present on the surface of some tumours, including breast cancer. Patients with high HER2 expression (IHC 3+ or IHC 2+/ISH+) are classified as HER2 positive and represent about 15-20% of breast cancer cases. Tumours previously deemed HER2 negative may still show some HER2 expression, with around 60-65% of HR-positive, HER2-negative cancers classified as HER2 low and about 25% as HER2 ultralow.
Endocrine therapies are typically used in the early treatment of HR-positive metastatic breast cancer. However, after two lines of endocrine therapy, their effectiveness often decreases, and chemotherapy becomes the standard care, although it generally shows poor response rates. Before ENHERTU's approval, there were no targeted therapies for patients with HER2 low or ultralow expression.
