Study: Enhertu shows promising results for HER2-low and HER2-ultralow metastatic breast cancer
Recent study results show that a new targeted treatment works better than standard chemotherapy for people with metastatic hormone receptor-positive breast cancers with low or ultralow HER2 status. (Posted 5/15/25)
RELEVANCE
Most relevant for: People with HR-positive metastatic breast cancer.
It may also be relevant for:
- people with breast cancer
Relevance: High
Strength of Science: High
What is this study about?
The main goal of this study was to see if treatment with Enhertu, a new , helped patients live longer without their cancer growing (progression-free survival). Findings from this study build on previous research suggesting a new way to classify breast cancers that were previously labeled as HER-negative. Some breast cancers in these new categories, called “HER2-low” and “HER2-ultralow,” may respond to a type of targeted therapy called anti-HER2 therapy.
Why is this study important?
This study provides new guidance for treating hormone receptor-positive () breast cancer. It also confirms the importance of categorizing cancers as HER2-low and HER2-ultralow to guide treatment.
is a protein that is sometimes found on the surface of breast cancer cells. Some breast cancer drugs work by targeting HER2 to block or slow cancer growth. Doctors decide whether to use these drugs based on lab tests that look at the level of HER2 on the surface of cancer cells—test results range from 0 to 3+. Breast cancers with high levels of HER2 (a score of 3+) were previously considered and could be treated with HER2-targeted treatments. Breast cancers with lower levels of HER2 (a score below 3) were considered to be and were not treated with HER2-targeted drugs.
In 2022, the DESTINY-04 study changed this understanding by demonstrating that study participants with HER2-low cancers (HER2 scores of 1+ or 2+) responded to the anti-HER2 drug Enhertu (trastuzumab deruxtecan, covered in previous XRAYs on DESTINY-04 and later approval).
Researchers in the DESTINY-06 study wanted to see if Enhertu can treat cancers with even lower levels of HER2: HER2-ultralow cancers that have a HER2 score above zero but below one This study compared Enhertu to chemotherapy as a treatment for hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer in those who had already tried hormone therapy.
Results of a test for HER2 status:
| Score is 0 | Tumor is HER2-negative |
| Score is more than 0, less than 1* | Tumor is HER2-ultralow |
| Score is 1+ or 2+ | Tumor is HER2-low |
| Score is 3+ | Tumor is HER2-positive |
Study findings
The DESTINY-06 study included 866 people with metastatic, HR+ breast cancer. Of these, 713 had HER2-low breast cancer and 153 had HER2-ultralow breast cancer. None had received prior chemotherapy, but most had already received at least two lines of hormone therapy for metastatic disease, including a CDK4/6 inhibitor.
Participants from 324 hospitals and cancer centers were randomly assigned to receive either Enhertu or one of three chemotherapy options: capecitabine, nab-paclitaxel or paclitaxel.
Overall, the researchers found that Enhertu is more effective than chemotherapy for both HER2-low and HER2-ultralow breast cancers.
Specifically, the researchers found that:
- Enhertu delayed cancer growth more effectively than chemotherapy: People with HER2-low breast cancer who were treated with Enhertu went 13.2 months without cancer growth compared to 8.1 months for people who received chemotherapy. The results for people with HER2-ultralow breast cancer were similar, although the test group was smaller.
- More people responded to Enhertu than chemotherapy: 57% of people with HER2-low cancers who took Enhertu had cancers that shrank or stopped growing, compared to 32% of people who received chemotherapy.
- Participants in both study groups experienced some side effects:
- People in the Enhertu group were more likely to have moderate-to-severe side effects. Slightly more than half (53%) of people who took Enhertu experienced a moderate or more serious side effect, compared to 44% in the chemotherapy group.
- The three most common side effects of Enhertu were nausea, fatigue and hair loss. In rare instances, the drug caused serious lung disease.
- The most common side effects reported by people in the chemotherapy group were fatigue, risk of infection (due to low white blood cell count) and painful swelling or pain in the hands and feet (hand-foot syndrome).
The research team continues to follow participants and will provide more information in the future on whether Enhertu helps participants live longer (improves overall survival).
