Frank Vinluan , 2025-04-21 17:36:00
A cancer drug from partners AstraZeneca and Daiichi Sankyo currently approved as a second-line or later treatment for metastatic breast cancer has interim clinical data showing it helped patients live longer without their disease worsening in the first-line setting, results that could support further expanding use of this targeted therapy.
AstraZeneca and Daiichi Sankyo are not disclosing specific details from the Phase 3 test in metastatic HER2-positive breast yet. But the companies said Monday that the planned interim analysis showed the drug, Enhertu, led to a “highly statistically significant and clinically meaningful improvement in progression-free survival.” That measure was made in comparison to a triple-drug combination currently used as a first-line treatment for this type of cancer. These results are important because many patients with metastatic breast cancer do not live long enough to receive a second line of treatment.
Enhertu is an antibody drug conjugate (ADC) that was discovered by Daiichi Sankyo and is being further developed and commercialized under a partnership with AstraZeneca. The antibody component of the drug targets HER2, a protein overexpressed on breast cancer cells. Enhertu was first approved by the FDA in 2019 as a third-line treatment for HER2-positive metastatic breast cancer. The therapy expanded its approved use to second-line treatment of this type cancer in 2022.
The interim results announced Monday are from a global Phase 3 test that enrolled 1,157 patients. Enhertu was tested by itself and in combination with pertuzumab, a Roche drug marketed under the brand name Perjeta. The study drug was compared to the chemotherapy Taxol combined with Perjeta and another Roche monoclonal antibody drug, Herceptin. This three-drug combination is a standard first-line treatment for metastatic HER2-positive breast cancer.
AstraZeneca and Daiichi Sankyo said the improvement in progression-free survival was observed across all pre-specified patient subgroups that received Enhertu paired with Perjeta. On the key secondary goal of measuring overall survival, the data are not yet mature. But the companies said interim overall survival data show a trend favoring the Enhertu combination compared to the standard three-drug regimen. A second cohort that is assessing Enhertu as a monotherapy compared to standard treatment remains blinded and will continue to the final analysis measuring progression-free survival.
“This is the first trial in more than a decade to demonstrate superior efficacy across a broad HER2-positive metastatic breast cancer patient population compared to the current first-line standard of care,” Susan Galbraith, executive vice president, oncology hematology R&D, AstraZeneca, said in a prepared statement. “This is a significant milestone for patients and sets the foundation for Enhertu in combination with pertuzumab as an important treatment option in the first-line HER2-positive setting.”
On safety, the companies said the results so far show the safety profile of the Enhertu and Perjeta combination is consistent with the known profiles of each therapy. Enhertu’s label carries a black box warning for the risk of interstitial lung disease. The companies said more data will be presented at an upcoming medical meeting and shared with regulators.
Under the terms of the partnership between AstraZeneca and Daichii Sankyo, the two companies share in the development of Enhertu globally except for Japan, where Daiichi Sankyo holds all rights to the ADC. The companies reported more than $3.7 billion in combined sales for the product in 2024, a more than 46% increase compared to sales of the drug in the prior year.
Public domain image by Stuart S. Martin, via the National Cancer Institute
