AstraZeneca and Daiichi Sankyo's Enhertu Demonstrates Significant Advances in Breast and Gastric Cancer Treatment

AstraZeneca and Daiichi Sankyo have unveiled groundbreaking results for their antibody-drug conjugate Enhertu (trastuzumab deruxtecan) in both breast and gastric cancers at the 2025 American Society of Clinical Oncology (ASCO) annual meeting. The data presented showcases Enhertu's potential to revolutionize treatment paradigms across multiple cancer types.

Enhertu Poised to Redefine First-Line HER2-Positive Breast Cancer Treatment

In the phase 3 Destiny-Breast09 trial, Enhertu combined with Roche's Perjeta (pertuzumab) demonstrated a significant improvement in progression-free survival (PFS) for patients with newly diagnosed HER2-positive breast cancer. The combination reduced the risk of disease progression or death by 44% compared to the current standard of care, a regimen known as THP (taxane, Herceptin, and Perjeta).

Dr. Rebecca Dent, deputy CEO (clinical) at National Cancer Center Singapore, stated that the Enhertu-Perjeta combination "represents a new first-line standard treatment option for HER2-positive breast cancer."

Key findings from the trial include:

• Median PFS of 40.7 months for Enhertu-Perjeta vs. 26.9 months for THP
• Two-year progression-free rate of 70% for Enhertu-Perjeta vs. 52% for THP
• Highly statistically significant improvement (p<0.00001)

The safety profile was consistent with previous studies, with similar rates of grade 3 or higher adverse events between the two arms. However, interstitial lung disease (ILD) remains a concern, occurring in 12.1% of patients receiving Enhertu-Perjeta compared to 1% in the THP arm.

Enhertu Solidifies Position in Second-Line Gastric Cancer Treatment

The Destiny-Gastric04 trial further established Enhertu's efficacy in HER2-positive gastric or gastroesophageal junction adenocarcinoma. In this study, Enhertu demonstrated superior overall survival compared to a combination of Eli Lilly's Cyramza (ramucirumab) and paclitaxel chemotherapy in patients who had progressed on first-line treatment.

Significant outcomes include:

• 30% reduction in the risk of death
• Median overall survival of 14.7 months with Enhertu vs. 11.4 months with Cyramza-paclitaxel
• 26% reduction in the risk of disease progression
• Objective response rate of 44% for Enhertu vs. 29% for Cyramza-paclitaxel

Dr. Pamela Kunz, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, described the results as "practice-validating" in the United States and "practice-changing" globally, positioning Enhertu as the preferred second-line treatment for HER2-positive gastric cancer.

Expanding Horizons and Future Directions

AstraZeneca and Daiichi Sankyo continue to explore Enhertu's potential across various treatment settings. Ongoing trials include:

• Destiny-Breast11: Evaluating Enhertu in presurgical HER2-positive early-stage breast cancer
• Destiny-Breast05: Investigating Enhertu in the postsurgical setting for breast cancer
• Destiny-Gastric05: Assessing Enhertu in first-line HER2-positive gastric cancer

As Enhertu solidifies its position across multiple indications, it has become one of AstraZeneca's fastest-growing oncology assets, with sales exceeding $3 billion in 2024. The pharmaceutical industry eagerly anticipates further developments as Enhertu continues to reshape the landscape of HER2-targeted therapies.