Positive high-level results from a planned interim analysis of the DESTINY-Breast09 Phase III trial showed Enhertu (trastuzumab deruxtecan) in combination with pertuzumab demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to a taxane, trastuzumab and pertuzumab (THP) as a 1st-line treatment for patients with HER2-positive metastatic breast cancer.

The PFS improvement was seen across all pre-specified patient subgroups with Enhertu in combination with pertuzumab. The key secondary endpoint of overall survival (OS) was not mature at the time of this planned interim analysis; however, interim OS data showed an early trend favouring the Enhertu combination compared with THP.

The second arm assessing Enhertu monotherapy versus THP remains blinded to patients and investigators and will continue to the final PFS analysis.

HER2-positive metastatic breast cancer is an aggressive disease driven by overexpression or amplification of HER2 affecting 15-20% of patients with metastatic breast cancer. While HER2-targeted therapies have improved outcomes, prognosis remains poor, with most patients experiencing disease progression within two years of 1st-line treatment with THP, which has been the standard of care for more than a decade. Further, approximately one in three patients never go on to receive treatment following 1st-line therapy due to disease progression or death.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “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 1st-line standard of care. 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.”

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “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."

The safety profile of Enhertu in combination with pertuzumab was consistent with the known profiles of each individual therapy.

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Data from the combination arm of DESTINY-Breast09 will be presented at an upcoming medical meeting and shared with regulatory authorities.

Enhertu is already approved in more than 75 countries as 2nd-line treatment for patients with HER2-positive breast cancer based on the results from the DESTINY-Breast03 trial.