Enhertu Promising for First-Line HER2-Positive Breast Cancer

AstraZeneca and Daiichi Sankyo have announced promising outcomes from their phase 3 trial of the antibody-drug conjugate Enhertu, scientifically known as trastuzumab deruxtecan, for patients with HER2-positive metastatic breast cancer. The DESTINY-Breast09 study is focused on assessing the effectiveness of Enhertu when combined with another drug, pertuzumab, as a first-line therapy.

HER2-positive metastatic breast cancer affects up to 20% of individuals with this disease type. While therapies targeting HER2 have improved patient outcomes over the years, the overall prognosis remains challenging. Most patients experience disease progression within two years of initiating standard treatments, which typically include a combination of taxane, trastuzumab, and pertuzumab (collectively referred to as THP).

Enhertu operates by targeting the HER2 protein present on the surface of cancer cells. This drug has received approval in over 75 countries to treat adults with HER2-positive breast cancer that is either non-operable or has metastasized and has been previously treated. In the recent DESTINY-Breast09 trial, the combination of Enhertu and pertuzumab demonstrated a significant improvement in progression-free survival compared to the traditional THP regimen. This positive outcome was consistent across various patient subgroups that were predefined in the study.

Although the interim data on overall survival revealed an initial trend favoring the Enhertu and pertuzumab combination over THP, this information was not fully mature at the time of the planned interim analysis. The safety profile of the Enhertu combination aligned with the known safety characteristics of the individual drugs involved.

These findings establish DESTINY-Breast09 as the first clinical trial in over ten years to showcase superior efficacy across a wide range of HER2-positive metastatic breast cancer patients when compared to the current standard of care. According to the companies, these results could redefine first-line treatment options for this patient group.

Susan Galbraith, who serves as the Executive Vice President of Oncology Hematology Research and Development at AstraZeneca, highlighted the significance of this milestone. She stated that the results lay a foundation for Enhertu, combined with pertuzumab, to become a crucial treatment avenue in first-line HER2-positive settings.

Ken Takeshita, the Global Head of Research and Development at Daiichi Sankyo, emphasized the importance of these results in effectively targeting HER2 to control disease progression early in the treatment process. He noted that building on the positive outcomes seen with Enhertu in second-line settings, these new findings indicate that initiating treatment with Enhertu and pertuzumab at the point of metastatic diagnosis can delay disease progression and extend the time before additional treatment becomes necessary.

The data from the combination arm of the DESTINY-Breast09 study will be shared with regulatory bodies for further review. The companies also mentioned that the section of the study evaluating Enhertu on its own versus the THP regimen remains blinded to patients.