Enhertu Plus Pertuzumab Redefines First-Line Treatment for HER2+ Metastatic Breast Cancer

Positive results from a planned interim analysis of the DESTINY-Breast09 Phase III trial showed that 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 first-line treatment for patients with HER2-positive metastatic breast cancer.

The DESTINY-Breast09 Phase III trial, led by AstraZeneca and Daiichi Sankyo, is the first in over a decade to show superior efficacy across a broad HER2-positive metastatic breast cancer population compared to the current first-line standard of care. As an innovative antibody-drug conjugate (ADC), Enhertu has the potential to redefine treatment approaches and improve outcomes for patients globally.

DESTINY-Breast09 is a global, randomized, multicenter, open-label trial involving 1,157 patients across five continents. The safety profile of this combination was consistent with the known profiles of each individual therapy, with no new safety concerns emerging during the interim analysis.

Dr. Ken Takeshita, Global Head of R&D at Daiichi Sankyo, emphasized the trial's significance: “The results 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."

Enhertu, uniquely combines a HER2-targeted monoclonal antibody with a potent topoisomerase I inhibitor payload (DXd), utilizing a sophisticated linker for precision delivery to cancer cells. Already approved in over 75 countries, Enhertu has shown robust efficacy and manageable safety profiles in previous studies across various HER2-positive and HER2-low cancers.

Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, highlighted the broader impact: “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.”

Breast cancer remains the second leading cause of cancer-related death worldwide, with more than two million new cases and approximately 665,000 deaths each year. Among these, HER2-positive breast cancer, which accounts for around 20% of diagnoses, is known for its aggressive nature and poor prognosis, particularly when metastatic.