Enhertu Plus Pertuzumab Redefines First-Line Standard in HER2 -Positive Metastatic Breast Cancer

A planned interim analysis of the Phase III DESTINY-Breast09 trial has shown promising results for Enhertu (trastuzumab deruxtecan) in combination with pertuzumab. The study found that this combination led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to the standard first-line treatment regimen of a taxane, trastuzumab, and pertuzumab (THP) in patients with HER2-positive metastatic breast cancer.

The improvement in PFS was observed consistently across all pre-specified patient subgroups receiving Enhertu and pertuzumab. Although the key secondary endpoint of overall survival (OS) was not mature at the time of this interim analysis, the early data suggest a favourable trend toward better OS outcomes with the Enhertu combination compared to THP. A second arm of the trial, which is evaluating Enhertu as a monotherapy against THP, remains blinded and will continue until the final PFS results are available.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, mentioned, “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, stated, “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.”

HER2-positive metastatic breast cancer is known for its aggressive nature, driven by overexpression or amplification of the HER2 gene. It affects approximately 15–20% of people with metastatic breast cancer. While HER2-targeted treatments have improved patient outcomes over the years, THP has remained the standard first-line therapy for more than ten years. Despite these treatments, the disease often progresses within two years, and around one-third of patients are unable to receive further therapy after first-line treatment due to disease progression or death.

The safety profile of the Enhertu and pertuzumab combination was in line with the known safety profiles of each individual drug. Enhertu is a HER2-directed DXd antibody-drug conjugate (ADC), developed by Daiichi Sankyo and jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. The data from this combination arm of the DESTINY-Breast09 trial will be presented at an upcoming medical conference and submitted to regulatory agencies for review. Enhertu is currently approved in more than 75 countries as a second-line treatment for HER2-positive breast cancer, based on earlier findings from the DESTINY-Breast03 trial.