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HER2 Low Metastatic Breast Cancer Phase 3 Results for ENHERTU Offer Potential to Redefine How the Disease is Classified and Treated

February 21, 2022 • 4:33 pm CST
(Vax Before Cancer)

Positive topline results from the pivotal DESTINY-Breast04 phase 3 clinical trial announced today showed ENHERTU® (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) in patients with HER2 low unresectable and/or metastatic breast cancer regardless of hormone receptor (HR) status versus physician's choice of chemotherapy, which is the current standard of care.

ENHERTU is a HER2-directed antibody-drug conjugate (ADC) jointly developed by Daiichi Sankyo and New Jersey-based AstraZeneca.

All patients in the trial received a HER2 test, and the results were centrally confirmed.

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors and is one of many biomarkers expressed in breast cancer tumors.

HER2 low status was defined as an immunohistochemistry (IHC) score of 1+ or IHC2+ with a negative in-situ hybridization (ISH) score.

HER2 expression is currently defined as either positive or negative.1 HER2 positive cancers are defined as IHC 3+ or IHC 2+/ISH+, and HER2 negative cancers are defined as IHC 0, IHC 1+, or IHC 2+/ISH-. 

Up to 55% of all patients with breast cancer have tumors with a HER2 IHC score of 1+ or a HER2 IHC score of 2+ in combination with a negative ISH test, an expression level not currently eligible for HER2 targeted therapy. 

Low HER2 expression occurs in both hormone receptor (HR) positive and HR negative disease.

HER2 testing is well-established to determine an appropriate treatment strategy in metastatic breast cancer.

Targeting the lower range of HER2 expression may offer another approach to delay disease progression and extend survival in patients with metastatic breast cancer. 

Currently, chemotherapy remains the only treatment option for patients with HR-positive tumors following progression on endocrine (hormone) therapy and for those who are HR negative.

"Today's historic news from DESTINY-Breast04 could reshape how breast cancer is classified and treated," said Susan Galbraith, MBBChir, Ph.D., Executive Vice President, Oncology R&D, AstraZeneca, in a press release issued on February 21, 2022.

"A HER2 directed therapy has never before shown a benefit in patients with HER2 low metastatic breast cancer."

"These results for ENHERTU are a huge step forward and could potentially expand our ability to target the full spectrum of HER2 expression, validating the need to change the way we categorize and treat breast cancer."

The companies stated the data will be presented at an upcoming medical meeting and shared with global health authorities.

Daiichi Sankyo is responsible for the manufacturing and supplying ENHERTU and datopotamab deruxtecan.

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