Enhertu Outperforms Chemotherapy in HER2-Low Unresectable/Metastatic Breast Cancer

Patients with HER2-low unresectable and/or metastatic breast cancer, regardless of HR status, tended to have improved outcomes with Enhertu (trastuzumab deruxtecan) compared to chemotherapy, according to findings from the phase 3 DESTINTY-Breast04 clinical trial.

The global, randomized, DESTINY-Breast04 trial met its main goal, which was improved progression-free survival (the time after treatment when a patient’s disease does not get worse) in pretreated patients with HR-positive, HER2-low metastatic breast cancer. Enhertu also met its secondary endpoint of improved progression-free survival in HER2-low metastatic breast cancer, regardless of HR status.

Overall survival was also improved with Enhertu over standard-of-care chemotherapy for both patients with HR-positive and HR-negative disease.

Another trial, DESTINY-Breast03, was presented in December 2021 and showed that treatment with Enhertu induced promising response rates in patients with HER2-positive metastatic breast cancer, including patients with brain metastases, leading one expert to suggest that the drug may become the standard of care in this patient population.

Then, earlier this year, the Food and Drug Administration (FDA) granted Enhertu a priority review for patients with unresectable or metastatic HER2-positive breast cancer who previously received an anti-HER2—based regimen. The FDA plans on reviewing data on the drug and deciding on if it will be granted an approval in this space sometime in the second quarter of 2022.

Enhertu is a HER2-directed antibody drug conjugate that works by binding to the HER2 protein on breast cancer cells and then kills tumor cells while leaving healthy (non-cancerous) cells intact.

“Today’s historic news from DESTINY-Breast04 could reshape how breast cancer is classified and treated. 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,” said Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, one of the companies that is developing Enhertu, in a statement.

DESTINY-Breast04 is an ongoing trial, and results will be presented at an upcoming oncology conference.

“Enhertu continues to redefine the treatment of HER2-targetable cancers. DESTINY-Breast04 is the first ever phase 3 trial of a HER2-directed therapy in patients with HER2-low metastatic breast cancer to show statistically significant and clinically meaningful benefit in progression-free and overall survival compared to standard treatment. We look forward to sharing the detailed findings of DESTINY-Breast04 with the medical community and initiating discussions with regulatory agencies globally with the goal of bringing Enhertu to patients with metastatic breast cancer previously considered to be HER2-negative,” said Ken Takeshita, global head, R&D, Daiichi Sankyo, the other co-developer of the drug, in a statement.

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