FDA Approval: Trastuzumab deruxtecan (Enhertu) for Breast Cancer

What the FDA actually approved

In 2019 the FDA gave Enhertu an accelerated approval. Its generic name is fam-trastuzumab deruxtecan-nxki. The file number is biologics license application 761139.

The approval letter gives the indication in one sentence. Enhertu is for adults with unresectable or metastatic HER2-positive breast cancer who have had two or more prior anti-HER2-based regimens in the metastatic setting.

Every clause there is a gate. Adults. Breast cancer that cannot be removed by surgery, or has already spread. HER2-positive on testing. And at least two HER2 treatments already given for advanced disease. The label has widened since. That was the group in 2019.

Approval at a glance

Field	Detail
Drug	Fam-trastuzumab deruxtecan-nxki (Enhertu)
Application	BLA 761139
Regulator	FDA
Year	2019
Class	Antibody-drug conjugate targeting HER2
Approval route	Accelerated approval
Basis	Tumor response rate and duration of response
Dose at approval	An intravenous infusion every 3 weeks, calculated from body weight

What an antibody-drug conjugate is

HER2 is a protein on the surface of some breast cancer cells. In HER2-positive breast cancer there is far more of it than normal. It drives the cancer to grow. Older HER2 drugs such as trastuzumab attach to that protein and block the signal.

An antibody-drug conjugate works another way. It uses the antibody as a delivery van. Enhertu is a HER2 antibody linked to a chemotherapy molecule. The antibody finds cells that carry HER2. It is drawn inside them. The chemotherapy is released there.

The point is concentration, not gentleness. A strong cell-killing drug lands mostly where the target is, rather than everywhere at once. It is still chemotherapy. It still has chemotherapy's side effects.

Whether any of this fits one person starts with a pathology report, not a drug name. Our page on biomarker testing explains how HER2 status is worked out.

The evidence the approval rested on

The FDA label describes the trial. DESTINY-Breast01 is registered as NCT03248492. It was a multicenter, single-arm study. It enrolled 184 female patients. All had HER2-positive breast cancer that could not be removed or had spread. All had already had two or more HER2 treatments.

These patients had been through a lot. The label records a median of five prior regimens for advanced disease. The range ran from two to seventeen. All had had trastuzumab and ado-trastuzumab emtansine. Two-thirds had had pertuzumab. The median age was 55.

An independent review committee assessed the results. The confirmed objective response rate was 60.3%. The 95% confidence interval ran from 52.9% to 67.4%. That splits into 4.3% complete responses and 56.0% partial ones. The median duration of response was 14.8 months.

Why "single-arm" matters

DESTINY-Breast01 had no comparison group. Everybody in it received Enhertu.

That design can show that tumors shrink. It cannot show that people lived longer than they would have on something else. There is no something else in the trial to measure against.

This is what accelerated approval is for. The approval letter says so plainly. The indication rests on tumor response rate and duration of response. Continued approval may depend on proof of benefit in a later trial. The FDA took an early measure — do the tumors shrink — so the drug could reach a group with few options left. The condition was that a proper randomized trial follow.

What it is like to take

Enhertu was approved at a weight-based infusion dose, worked out for each person by the treating team. It is an infusion into a vein once every three weeks. It carries on until the disease grows or the side effects become too much.

The label carries a boxed warning. That is the FDA's strongest, and it covers two things. The first is interstitial lung disease. That means inflammation and scarring of lung tissue, and the label notes it has included fatal cases. A new or worse cough, breathlessness or fever needs reporting the same day. The second is harm to a developing fetus.

The label also flags low neutrophil counts and weaker heart pumping. Either may mean pausing, reducing or stopping the drug.

What this does and doesn't change

Some people with HER2-positive breast cancer had already been through the standard HER2 drugs. For them the shelf was nearly empty. This added a real option. Six in ten tumors shrank in a group that had run out of choices.

As the label stood in 2019, it changed nothing for HER2-negative disease. It changed nothing for early breast cancer treated with surgery. And it did not reduce the need for accurate HER2 testing.

What to keep in perspective

• A response rate is not a survival figure. Sixty percent of tumors shrinking is not sixty percent of people living longer. The trial was not built to answer the second question.
• Accelerated approval is provisional by design. Labels move as confirmatory data arrive, in both directions.
• The trial group was narrow. Adults, HER2-positive, heavily pre-treated, and well enough to enroll. People sicker than that were not studied.
• Interstitial lung disease is uncommon but serious. Knowing about it is useful mainly because it makes you quick to report symptoms.

Questions worth asking

• Does my pathology report actually say HER2-positive, and by which test?
• Which HER2 treatments have I already had, and where does this sit in the sequence?
• What symptoms should make me call the team the same day?

Our guides to breast cancer and targeted therapy cover the background in plain language.

Sources

• FDA approval letter, BLA 761139 (ENHERTU)
• FDA prescribing information (2019): ENHERTU
• FDA Drugs@FDA overview: ENHERTU, BLA 761139
• NCI PDQ: Breast Cancer Treatment (Health Professional Version)

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

Cancer Explained is published by the National Cancer Information Foundation. It is not medical advice and does not suggest a test or treatment.

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