AstraZeneca and Daiichi Sankyo's Enhertu Shows Promise in First-Line Breast Cancer Treatment

AstraZeneca and Daiichi Sankyo have announced groundbreaking results from their Phase III DESTINY-Breast09 trial, potentially reshaping the treatment landscape for HER2-positive metastatic breast cancer. The study, which evaluated the antibody-drug conjugate Enhertu, demonstrated significant efficacy improvements over the current standard of care.

DESTINY-Breast09 Trial Results

The DESTINY-Breast09 trial tested Enhertu, both alone and in combination with Roche's Perjeta, against the current standard THP regimen (taxane chemotherapy, Herceptin, and Perjeta) in first-line HER2-positive metastatic breast cancer patients. Key findings include:

• A "highly statistically significant and clinically meaningful improvement" in progression-free survival (PFS) for the Enhertu-Perjeta combination compared to THP.
• PFS benefits were observed across various patient subgroups.
• While overall survival data were not mature at the time of analysis, early trends favored the Enhertu regimen.
• The safety profile was consistent with known side effects of the individual agents.

Susan Galbraith, EVP of oncology hematology R&D at AstraZeneca, stated, "DESTINY-Breast09 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 first-line standard of care."

Potential Impact on Treatment Paradigm

Analysts at Leerink Partners suggest that these findings could lead to a significant shift in the treatment of HER2-positive metastatic breast cancer. They noted that physicians appear "enthusiastic about Enhertu entering the frontline." However, safety considerations, particularly the risk of interstitial lung disease (ILD), may play a crucial role in determining the drug's clinical value and adoption rate.

The DESTINY-Breast09 results build upon earlier promising data from the phase 1/2 DESTINY-Breast07 trial, which showed an 84% confirmed tumor response rate and an 89.4% 12-month progression-free survival rate for the Enhertu-Perjeta combination in the first-line setting.

Regulatory Outlook and Commercial Performance

AstraZeneca and Daiichi Sankyo are preparing regulatory submissions based on the DESTINY-Breast09 results. The partners plan to present detailed findings at an upcoming medical conference and engage with health authorities.

Enhertu has already seen significant commercial success, with combined sales reaching $3.75 billion in 2024, up from $2.57 billion the previous year. The drug has secured multiple approvals, including:

• A January 2025 FDA approval for metastatic or unresectable breast cancer with ultralow HER2 expression levels.
• European Union approval for HR-positive, HER2-low or HER2-ultralow metastatic breast cancer.
• Promising results in gastric cancer, potentially supporting expansion into this indication.

As the pharmaceutical industry eagerly awaits full data disclosure, the DESTINY-Breast09 results may herald a new era in the treatment of HER2-positive metastatic breast cancer, potentially establishing Enhertu as a new standard of care in the first-line setting.