ENHERTU® Shows 13.2 Months Median PFS in HR Positive, HER2 Low/Ultralow Metastatic Breast Cancer Post-Endocrine Therapy

In an important development for breast cancer treatment, the DESTINY-Breast06 phase 3 trial has revealed that ENHERTU® (trastuzumab deruxtecan) significantly improves progression-free survival (PFS) compared to standard chemotherapy in patients with HR positive, HER2 low or ultralow metastatic breast cancer. These findings were presented at the 2024 American Society of Clinical Oncology Annual Meeting.

Developed by Daiichi Sankyo and AstraZeneca, ENHERTU is a HER2 directed DXd antibody drug conjugate (ADC). In the study, patients who had previously undergone endocrine therapy saw a 38% reduction in the risk of disease progression or death when treated with ENHERTU, achieving a median PFS of 13.2 months versus 8.1 months for those on chemotherapy.

The trial's key secondary endpoint also showed a 37% reduction in disease progression or death risk in the overall trial population. This significant benefit was consistent across patients with HER2 low and HER2 ultralow expressions. Specifically, for patients with HER2 ultralow expression, ENHERTU resulted in a 22% reduction in disease progression risk.

Additionally, the objective response rate (ORR) was notably higher with ENHERTU. For HER2 low expression patients, the confirmed ORR was 56.5%, including nine complete responses (CRs) and 194 partial responses (PRs), compared to 32.2% in the chemotherapy group with no complete responses. In the overall trial population, the confirmed ORR was 57.3% for ENHERTU.

The safety profile of ENHERTU was consistent with previous clinical trials. The most common adverse events were neutropenia (20.7%), leukopenia (6.9%), and anemia (5.8%). Interstitial lung disease (ILD) or pneumonitis occurred in 11.3% of patients, mostly low-grade.

Dr. Giuseppe Curigliano, Principal Investigator for the trial, highlighted the limited efficacy of further endocrine-based therapy after initial treatments, emphasizing that ENHERTU could become a new standard of care for patients with HER2 low and HER2 ultralow expressing tumors after endocrine therapy.

Ken Takeshita, MD, Global Head of R&D at Daiichi Sankyo, and Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, both noted the potential of ENHERTU to significantly impact the treatment landscape for HER2 expressing metastatic breast cancer.

Further supporting ENHERTU's efficacy, updated results from the DESTINY-Breast03 phase 3 trial demonstrated a meaningful survival improvement over trastuzumab emtansine (T-DM1) in HER2 positive metastatic breast cancer patients. The median overall survival (OS) was 52.6 months for the ENHERTU group versus 42.7 months for the T-DM1 group.

Interim results from the DESTINY-Breast07 phase 1b/2 trial also showed promising activity of ENHERTU as a first-line treatment, both as a monotherapy and in combination with pertuzumab, for HER2 positive metastatic breast cancer. The confirmed ORR was 76.0% for ENHERTU alone and 84.0% when combined with pertuzumab.

ENHERTU's safety profile, both as a monotherapy and in combination, was consistent with known safety profiles, demonstrating manageable adverse events and no new safety concerns.

The DESTINY-Breast06 trial enrolled 866 patients globally, assessing the efficacy and safety of ENHERTU versus investigator’s choice of chemotherapy. The primary endpoint was PFS in the HR positive, HER2 low population, with secondary endpoints including PFS, OS, ORR, duration of response (DOR), and safety.

Breast cancer remains a major global health challenge, with HER2 expression playing a critical role in the disease's progression and treatment. ENHERTU's significant benefits in progression-free survival and response rates represent a promising advancement in the treatment of HER2 low and ultralow expressing metastatic breast cancer, offering new hope for improved patient outcomes.

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