Results of a randomized, phase 3 study presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated that combining trastuzumab deruxtecan (Enhertu) with pertuzumab (Perjeta) can delay cancer growth for people with HER2-positive advanced breast cancer longer than the current standard treatment.
What Is HER2-Positive Breast Cancer?
- HER2-positive breast cancer makes up about 15% to 20% of all breast cancers.
- These cancers tend to grow and spread faster than other types.
- While targeted therapies have improved outcomes, most patients with advanced disease see their cancer progress within two years of starting first-line treatment.
About the DESTINY-Breast09 Study
- Who was studied?
1,157 patients with HER2-positive, locally advanced or metastatic breast cancer who had not received prior chemotherapy or HER2-targeted therapy. - What treatments were compared?
- Trastuzumab deruxtecan + pertuzumab
- The current standard: taxane chemotherapy + trastuzumab + pertuzumab (THP)
Key Results
- Longer time before cancer growth:
- Patients on trastuzumab deruxtecan + pertuzumab had a median progression-free survival (PFS) of over 3 years (40.7 months).
- Those on the standard THP treatment had a median PFS of just over 2 years (26.9 months).
- Reduced risk:
- The new combination reduced the risk of cancer progression or death by 44% compared to the standard treatment.
- More patients remained cancer-free at 2 years:
- 70% of patients on the new combo had no cancer growth at 2 years, versus 52% on the standard treatment.
- Better tumor response:
- 85% of patients on the new combo saw their tumors shrink or disappear, compared to 78.6% on the standard.
- 15% had no signs of cancer after treatment, compared to 8.5% on the standard.
- Side effects:
- Both groups had similar rates of serious side effects.
- Nausea, vomiting, and constipation were more common with the new combo.
- Interstitial lung disease (a known risk) occurred in about 12% of patients on the new combo, but most cases were not severe.
What’s Next?
- Researchers will continue to follow patients to see if the new combination also helps them live longer overall.
- The study is ongoing, and more data on long-term survival and side effects will be reported in the future.
What This Means for Patients
This new drug combination could become the new standard first treatment for people with advanced HER2-positive breast cancer, offering longer control of the disease and hope for better outcomes. If you or a loved one has HER2-positive advanced breast cancer, talk to your care team about the risks and benefits of all treatment options.
About Enhertu
Antibody drug conjugates (ADCs) are a type of targeted cancer medicine that deliver a cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Enhertu is comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor (DXd) payload by a tetrapeptide linker. It is designed to deliver enhanced cell destruction upon release inside the cell and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.
Enhertu has a black box warning for interstitial lung disease and embryo-fetal toxicity. Enhertu is also FDA approved for appropriate patients with NSCLC, gastric or gastroesophagela junction cancer, and appropriate patients with HER2-positive solid tumors. Enhertu is FDA approved for the treatment of adult patients with unresectable or metastatic:
- HER2-positive breast cancer who have received a prior anti-HER2-based regimen in the metastatic setting or in the neoadjuvant/adjuvant setting in appropriate patients after recurrence.
- HR-positive HER2-low or HER2-ultralow breast cancer as determined by an FDA-approved test that has progressed on one or more endocrine therapies in the metastatic setting
- HER2-low breast cancer as determined by an FDA-approved test who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of adjuvant chemotherapy.
- Appropriate patients with HER2-positive gastric cancer, non-small cell lung cancer, and other solid tumors.
More Reading
Understanding HER2+Breast Cancer
Enhertu (Trastuzumab Deruxtecan) Treatment of HER2+ Breast Cancer
Join the Conversation on CancerConnect!
Reference
Tolaney SM, Jiang Z, Zhang O, et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09. JCO. 2025;43:S17. LBA1008.
