FDA Approval: Ado-trastuzumab emtansine (Kadcyla) for Breast Cancer

An antibody with a warhead attached

Ado-trastuzumab emtansine is sold as Kadcyla. FDA records show its original approval on February 22, 2013, under priority review.

The idea behind it is simple to state. Take an antibody that already finds one kind of cancer cell. Chain a chemotherapy drug to it. The antibody does the aiming, and the drug only gets released where the antibody lands.

Here the antibody is trastuzumab, which binds the HER2 protein. The attached drug is DM1, which blocks microtubules, the scaffolding a cell needs to divide. The label calls the whole thing a HER2-targeted antibody and microtubule inhibitor conjugate.

Why HER2 matters

HER2 is a protein on the surface of some breast cancer cells. When there is too much of it, the cell is pushed to grow.

NCI lists HER2 status as one of the biomarkers used to sort breast cancer, alongside the estrogen and progesterone receptors. The label is strict about proving it. Tumor samples must show 3+ on immunohistochemistry, or an amplification ratio of 2.0 or higher on in-situ hybridization, tested at a central laboratory.

That is not a formality. The drug has nothing to aim at otherwise. Our page on HER2-positive and HER2-low breast cancer explains what the report says, and our page on biomarker testing covers why the test comes first.

What the label covers

There are two indications, both as a single agent.

The first is HER2-positive metastatic breast cancer in people who already had trastuzumab and a taxane. They must have had prior therapy for metastatic disease, or the cancer must have come back during or within six months of finishing adjuvant treatment.

The second is adjuvant treatment of HER2-positive early breast cancer where invasive disease is still present after neoadjuvant taxane and trastuzumab-based treatment.

It is given by drip every 3 weeks, with the amount calculated from body weight. For early breast cancer, that runs for 14 cycles. The label sets a ceiling the team must not go above, and says the drug must never be swapped for ordinary trastuzumab.

The two trials

EMILIA tested it in advanced disease. It randomized 991 people with HER2-positive advanced or metastatic breast cancer to Kadcyla, or to lapatinib plus capecitabine.

Median progression-free survival was 9.6 months against 6.4 months, a hazard ratio of 0.65. Overall survival was also better: a median of 30.9 months against 25.1, with a hazard ratio of 0.68.

KATHERINE tested a different question. It enrolled 1,486 people whose HER2-positive early breast cancer still showed invasive tumor after neoadjuvant treatment and surgery. They received Kadcyla or trastuzumab for 14 cycles.

An invasive disease-free survival event occurred in 12.2 percent against 22.2 percent, a hazard ratio of 0.50. At three years, 88.3 percent were event-free against 77.0 percent. Overall survival improved too, with a hazard ratio of 0.66.

The boxed warning

The label carries a boxed warning, the strongest kind FDA uses. It names three things.

Liver injury. Serious hepatotoxicity has been reported, including liver failure and death. Transaminases and bilirubin are checked before starting and before every dose.

Heart. The drug can lower left ventricular ejection fraction, the share of blood the heart pushes out with each beat. Heart function is measured before treatment and monitored during it.

Pregnancy. Exposure during pregnancy can harm a fetus, and effective contraception is advised.

Beyond the box, the label warns about lung toxicity. Interstitial lung disease or pneumonitis means stopping the drug permanently. It also warns about infusion reactions, low platelets, and nerve damage in the hands and feet.

Patients are told to seek help straight away for signs of acute hepatitis: nausea, vomiting, pain in the upper right side of the abdomen, jaundice, dark urine, widespread itching, or loss of appetite.

When to get checked

This drug is for people already diagnosed. The step before that is noticing a change. NCI lists what to bring to a doctor:

• A lump in or near the breast, or under the arm.
• A thick or firm area in the same places.
• A change in the size or shape of a breast.
• Discharge from the nipple that is not breast milk.
• A nipple that changes shape, flattens, or points differently.
• Scaly or swollen skin, redness or darkening, or itching on the breast, nipple or areola.

NCI is direct that early breast cancer often has no symptoms at all, which is why screening exists alongside this list. Our page on mammograms covers what the appointment involves.

The group picture

SEER figures describe the whole United States population, not one person, and they cover all breast cancer rather than the HER2-positive subset.

Five-year relative survival for female breast cancer is 91.9 percent for cases from 2016 to 2022. By stage it is 100.0 percent while confined to the breast, 87.5 percent once it reaches nearby lymph nodes, and 33.8 percent once it has spread further.

Sixty-four percent are found at that first stage. An estimated 321,910 new cases and 42,140 deaths are projected for 2026, and the median age at diagnosis is 64.

What this approval cannot tell you

It cannot tell you whether this drug fits a particular person. That turns on HER2 status, what treatment came before, liver function, heart function and lung history.

It cannot promise the trial result to an individual. A hazard ratio of 0.50 describes 1,486 people over years, not one outcome.

And it does not describe HER2-negative breast cancer at all. Without the target, the antibody has nowhere to land.

Sources

• DailyMed, KADCYLA (ado-trastuzumab emtansine) prescribing information — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e
• FDA Drugs@FDA, ado-trastuzumab emtansine (BLA 125427) — https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125427
• openFDA Drugs@FDA API, BLA125427 submission record (ORIG-1, 2013-02-22, priority review) — https://api.fda.gov/drug/drugsfda.json?search=openfda.application_number:%22BLA125427%22&limit=1
• NCI, Breast Cancer Signs and Symptoms — https://www.cancer.gov/types/breast/symptoms
• NCI PDQ, Breast Cancer Treatment (Health Professional Version) — https://www.cancer.gov/types/breast/hp/breast-treatment-pdq
• SEER Cancer Stat Facts, Female Breast Cancer — https://seer.cancer.gov/statfacts/html/breast.html

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.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

See an error, old source, or unclear wording? Tell us.