AstraZeneca (AZ) and Daiichi Sankyo have shared positive results from a late-stage study of their antibody drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) in patients with HER2-positive metastatic breast cancer.
The phase 3 DESTINY-Breast09 study has been evaluating the drug in combination with pertuzumab as a first-line treatment for this patient population.
Up to 20% of patients with metastatic breast cancer are affected by HER2-positive disease. Despite HER2-targeted therapies improving outcomes, prognosis remains poor, with the majority of patients experiencing disease progression within two years of first-line treatment with standard-of-care taxane, trastuzumab and pertuzumab (THP).
Enhertu, which targets HER2 on cancer cells, is already approved in more than 75 countries globally to treat adults with pre-treated unresectable or metastatic HER2-positive breast cancer.
In DESTINY-Breast09, Enhertu plus pertuzumab demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival compared to THP, with this benefit seen across all pre-specified patient subgroups.
Interim overall survival data also showed an early trend favouring Enhertu plus pertuzumab compared to THP, but this was not mature at the time of the planned interim analysis. The safety profile of the Enhertu combination was consistent with the known profiles of the individual therapies.
The results make DESTINY-Breast09 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, according to the companies.
Susan Galbraith, executive vice president, oncology haematology research and development, AZ, said the results mark a “significant milestone for patients and [set] the foundation for Enhertu in combination with pertuzumab as an important treatment option in the first-line HER2-positive setting.”
Ken Takeshita, global head, research and development, Daiichi Sankyo, added: “The results from DESTINY-Breast09 reinforce the importance of effectively targeting HER2 to achieve durable disease control early in the treatment of HER2-positive metastatic breast cancer.
“Building on the positive results seen with Enhertu in the second-line setting, these new findings suggest that starting treatment with Enhertu in combination with pertuzumab at the time of metastatic diagnosis delays disease progression, postponing the time until additional treatment may be needed.”
Data from the combination arm of DESTINY-Breast09 will be shared with regulatory authorities, the companies outlined, adding that the second arm evaluating Enhertu monotherapy versus THP remains blinded to patients.