Who is this trial for?
This trial was for people with HER2-positive breast cancer who still had cancer present at surgery after their pre-surgery treatment — a sign of higher risk that it could return.
People in the trial had:
- HER2-positive breast cancer — the cancer makes too much of a growth protein called HER2.
- Pre-surgery (neoadjuvant) treatment first, then surgery — and cancer was still found in the breast or lymph nodes at surgery (called residual disease). This is the key point: residual disease signals a higher risk of the cancer returning.
What kind of trial is this?
This trial looked at how to prevent the cancer coming back after surgery, by using a stronger after-surgery drug in people at higher risk.
Background: why researchers asked this question
People whose HER2-positive cancer is still present at surgery (after pre-surgery treatment) are at higher risk of it returning. For years, the standard after-surgery treatment for this group has been a targeted drug called T-DM1.
A newer targeted drug, T-DXd, had already proven more powerful against HER2-positive cancer that had spread. Researchers asked: in this high-risk after-surgery setting, would switching from T-DM1 to T-DXd lower the chance of the cancer returning even further?
The trial: what was tested and how
DESTINY-Breast05 enrolled 1,635 people with high-risk, residual HER2-positive breast cancer. Each was assigned at random to one of two after-surgery treatments, given by IV:
- T-DXd (the newer drug), or
- T-DM1 (the current standard).
Researchers measured how many people stayed free of invasive cancer over time (invasive disease-free survival), and watched closely for side effects — especially a known lung problem linked to T-DXd. Everyone knew which drug they were getting (“open-label”).
A note before the results
T-DXd has revolutionized our treatment of breast cancer in the metastatic setting, and it comes as no surprise that the drug is now being tested in the adjuvant setting. However, unlike stage IV breast cancer — where we know our treatments will never lead to a permanent remission — we are a bit more wary of potential treatment harm in the adjuvant, or curative, setting.
Therefore, although this trial is important and is changing practice, we are always mindful of the dangers of T-DXd, since the side effects can be life-threatening.
Results: what they found
The newer drug clearly lowered the chance of the cancer returning — but it came with an important safety trade-off.
T-DXd (newer) vs T-DM1 (standard)
A large difference. The newer drug roughly halved the chance of the cancer returning over this period.
Lung inflammation was far more common with T-DXd, but most cases were mild (grade 1–2) and most people recovered. Serious cases were uncommon (about 1%) — though two people died, which is why careful monitoring, and promptly reporting any new cough or breathlessness, really matters.
The most frequent was nausea (about 7 in 10 people), along with constipation, vomiting, and low neutrophil counts. Nausea is usually controlled with anti-sickness medicines, which are recommended before each dose. By comparison, T-DM1 more often raised liver-enzyme levels and lowered platelet counts.
It is still too early to know whether people simply live longer with T-DXd — those results aren't mature yet. So far the benefit is measured in fewer cancer returns.
The bottom line
For people with high-risk HER2-positive breast cancer who still had cancer at surgery after pre-surgery treatment, switching the after-surgery drug from T-DM1 to T-DXd roughly halved the chance of the cancer coming back. But T-DXd carries a serious lung-inflammation risk that needs careful monitoring.
What this could mean for you
- A meaningful gain for a high-risk group. Fewer cancers came back with the newer drug.
- The lung risk is real. Anyone on T-DXd should report a new or worsening cough, shortness of breath, or fever promptly — early action matters.
- Long-term survival isn't yet known. The trial hasn't yet shown whether it helps people live longer overall.
Who should interpret this
These results describe a study group, not any one person, and come from an early (interim) look at the trial. Your oncology team can weigh the benefit against the lung risk for your situation. A note on the evidence: this trial was funded by the companies that make T-DXd, and everyone knew which drug they were getting.
Questions & comments
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