Key points
- Trastuzumab emtansine (Kadcyla) is trastuzumab with an anticancer drug attached, so that the drug goes straight to HER2-positive cells [1].
- It is used in HER2-positive breast cancer: after surgery when some tumour was still left, and in disease that has spread [1].
- If some tumour is still left after treatment before surgery, Kadcyla prevented the cancer from coming back better than trastuzumab; with Kadcyla, recurrence at 3 years was roughly halved [1, 2].
- Three important risks: liver damage, a weakened heart and harm to an unborn baby; a liver test is done before each infusion [1].
- Low platelets and mild bleeding (such as nosebleeds) are common [1].
What is this drug and how does it work?
For physicians
Trastuzumab emtansine (in the United States ado-trastuzumab emtansine; abbreviated T-DM1), brand name Kadcyla, is an anti-HER2 antibody-drug conjugate (ADC) [1]. In this drug, the antibody trastuzumab is joined through a stable linker to DM1 (a maytansine derivative that disrupts the cell's microtubules); on average 3.5 DM1 molecules sit on each antibody [1].
After binding to HER2, Kadcyla enters the tumour cell and is broken down in lysosomes; the released DM1 binds to tubulin, disrupts the microtubule network and causes cell division arrest and cell death [1]. In laboratory studies, Kadcyla, like trastuzumab, also inhibits HER2 signalling and recruits immune cells to attack the cancer cell [1].
Kadcyla must not be substituted for trastuzumab (Herceptin) [1].
Which cancers is it used for?
According to the FDA label, Kadcyla is approved only for HER2-positive breast cancer, and patients should be selected on the basis of a validated HER2 test on a tumour sample [1]. In recent years, trastuzumab deruxtecan (Enhertu) has given better results than Kadcyla in head-to-head comparisons, both in metastatic disease [3] and in residual disease after treatment before surgery [4], and is approved for both settings in its FDA label [5]. The choice between these drugs depends on each patient's situation, and approval status may differ between countries.
Your doctor may prescribe this drug for:
- HER2-positive breast cancer — that has spread [1, 6]
- Early HER2-positive breast cancer — adjuvant treatment (after surgery) [1, 2]
Whether it suits you depends on the type and stage of your cancer and your test results. Details of each use are in the section for doctors.
For physicians
| Cancer | Conditions of use | Key evidence |
|---|---|---|
| HER2-positive breast cancer — metastatic | Single agent, in patients who have previously received trastuzumab and a taxane (separately or together) and have either been treated for metastatic disease or relapsed during or within 6 months of adjuvant treatment [1] | EMILIA [6]: vs lapatinib + capecitabine, median progression-free survival 9.6 vs 6.4 months (HR 0.65) and median overall survival 30.9 vs 25.1 months (HR 0.68) [1] |
| Early HER2-positive breast cancer — adjuvant treatment (after surgery) | Single agent, in patients with residual invasive disease after neoadjuvant taxane- and trastuzumab-based treatment; 14 cycles [1] | KATHERINE [2]: 3-year invasive disease-free survival 88.3% vs 77.0% with trastuzumab (HR 0.50) and HR for overall survival 0.66 [1] |
The main source for the table is the FDA label for Kadcyla.
How it is given and dose
Kadcyla is given as an intravenous infusion (drip) once every 3 weeks (a 21-day cycle) at the treatment centre [1]. The first infusion takes 90 minutes, and you are observed for at least 90 minutes afterwards for fever, chills or other reactions; later infusions, if well tolerated, take 30 minutes, with observation for at least 30 minutes [1]. The infusion site is checked during the infusion for leakage of the drug under the skin [1].
- Length of treatment: in early breast cancer, 14 cycles in total unless the cancer comes back or side effects become unmanageable; in metastatic disease, until the disease progresses or side effects become unmanageable [1].
- Before starting: an HER2 test, liver enzyme and bilirubin tests, a platelet count, a measurement of heart function (LVEF) and, in women who could become pregnant, a check of pregnancy status [1].
- During treatment: liver enzymes, bilirubin and platelets before each dose, and LVEF measurements at regular intervals (for example every 3 months) [1].
Before starting and before each dose: transaminases and bilirubin, platelet count; LVEF before starting and during treatment; HER2 with an approved test; pregnancy test [1].
Administration: do not substitute with trastuzumab (check the vial label). Reconstitute, then dilute in 250 mL of 0.9% sodium chloride (5% dextrose must not be used); 0.2 or 0.22 micron PES in-line filter; not as a push or bolus [1].
Interactions: avoid strong CYP3A4 inhibitors (list in the section Interactions, pregnancy and precautions); if possible, delay treatment until about 3 half-lives after they are stopped, otherwise monitor closely for toxicity [1].
For physicians
Dose and schedule (FDA label)
Early breast cancer with residual disease (KATHERINE)
HER2-positive, residual invasive disease after neoadjuvant treatment with a taxane and trastuzumab
HER2-positive, residual invasive disease after neoadjuvant treatment with a taxane and trastuzumab
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab emtansine (Kadcyla) | 3.6 mg/kg (never more) | IV infusion; initial 90 minutes, then 30 minutes if tolerated | Day 1 |
Evidence: KATHERINE (2025), KATHERINE (2019)
Metastatic breast cancer
HER2-positive, after previous trastuzumab and a taxane (or relapse during or within 6 months of adjuvant treatment)Cycle length: Every 3 weeks
HER2-positive, after previous trastuzumab and a taxane (or relapse during or within 6 months of adjuvant treatment)
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab emtansine (Kadcyla) | 3.6 mg/kg (never more) | IV infusion; initial 90 minutes, then 30 minutes if tolerated | Day 1 |
Evidence: EMILIA (2012)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Infusion: observe for at least 90 minutes after the first dose and 30 minutes after later doses; monitor the infusion site for extravasation. Infusion reaction: slow or interrupt; life-threatening reaction: stop permanently [1].
Delayed or missed dose: give as soon as possible; keep a 3-week interval from then on [1].
Kidney and liver: CLcr 30 to 89 mL/min and mild or moderate hepatic impairment: no starting dose adjustment; there are insufficient data for CLcr below 30 and severe hepatic impairment [1].
Monitoring: signs of ILD and bleeding; peripheral neuropathy [1].
| Adverse reaction | Metastatic breast cancer | Early breast cancer |
|---|---|---|
| Raised transaminases | Grade 2 (above 2.5 to 5 × ULN): same dose. Grade 3 (above 5 to 20 ×): hold until grade 2 or less, then one level lower. Grade 4: stop [1] | ALT grade 2 to 3 (above 3 to 20 ×): hold until grade 1 or less, then one level lower. AST grade 2 (above 3 to 5 ×): hold until grade 1, same dose; AST grade 3: hold until grade 1, one level lower. Grade 4: stop [1] |
| Raised bilirubin | Grade 2 (above 1.5 to 3 ×): hold until grade 1 or less, same dose. Grade 3 (above 3 to 10 ×): hold until grade 1, one level lower. Grade 4: stop [1] | Above 1 to 2 × ULN on the day of dosing: hold until 1 × ULN or less, one level lower. Above 2 × at any time: stop [1] |
| Drug-induced liver injury or NRH | Transaminases above 3 × with bilirubin above 2 × ULN without another cause, or nodular regenerative hyperplasia (any grade): stop permanently [1] | Same [1] |
| Thrombocytopenia | Grade 3 (25,000 to below 50,000): hold until 75,000 or more, same dose. Grade 4 (below 25,000): hold until 75,000, one level lower [1] | Grade 2 to 3 on the day of dosing (25,000 to below 75,000): hold until 75,000, same dose (after 2 delays, consider reducing by one level). Grade 4: hold until 75,000, one level lower [1] |
| Decreased LVEF | LVEF below 40%: hold and repeat within 3 weeks; if confirmed, stop. 40 to 45% with a fall of 10 points or more: hold; if it does not recover to within 10 points of baseline within 3 weeks, stop. 40 to 45% with a fall of less than 10 points: continue and repeat within 3 weeks. Symptomatic heart failure: stop [1] | LVEF below 45%: hold and repeat within 3 weeks; if confirmed, stop. 45 to below 50% with a fall of 10 points or more: hold; if it does not recover, stop. 45 to below 50% with a fall of less than 10 points: continue and repeat within 3 weeks. Symptomatic heart failure or grade 3 to 4, or grade 2 with LVEF below 45%: stop [1] |
| Lung | ILD or pneumonitis: stop permanently [1] | ILD or pneumonitis: stop permanently. Grade 2 radiation pneumonitis not improving with treatment, or grade 3 to 4: stop [1] |
| Peripheral neuropathy | Grade 3 to 4: hold until grade 2 or less [1] | Grade 3 to 4: hold until grade 2 or less [1] |
Dose levels: 3.6 → 3 → 2.4 mg/kg; if a further reduction is needed: stop; do not re-escalate after a reduction [1].
Side effects
For physicians
In a total of 884 patients with HER2-positive metastatic breast cancer who received Kadcyla alone, the most common side effects (25% or more) were fatigue, nausea, musculoskeletal pain, haemorrhage, thrombocytopenia, headache, raised liver enzymes, constipation and nosebleeds [1].
In the KATHERINE trial (adjuvant treatment), the frequency of the most common side effects in the Kadcyla group vs the trastuzumab group was [1]:
- Fatigue: 50% vs 34%
- Nausea: 42% vs 13%
- Raised liver enzymes (transaminases): 32% vs 8%
- Musculoskeletal pain: 30% vs 29%
- Haemorrhage: 29% vs 10%
- Thrombocytopenia: 29% vs 2.4%
- Headache: 28% vs 17%
- Peripheral neuropathy (numbness or tingling in the hands and feet): 28% vs 14%
- Joint pain: 26% vs 21%
- Nosebleeds: 22% vs 3.5%
In KATHERINE, 26% of patients in the Kadcyla group had a grade 3 or higher adverse reaction (vs 15% with trastuzumab), and 18% stopped treatment because of side effects [1].
Serious side effects
These side effects are less common but serious; if you notice any sign of them, tell your team early:
- Liver damage: yellowing of the skin or eyes, dark urine or pain on the right side of the abdomen; a liver test is done before each infusion [1].
- A weakened heart: shortness of breath, swollen legs or palpitations [1].
- Serious bleeding: a severe headache, vomiting blood or black stools, especially when platelets are low [1].
- Lung damage: a new cough or shortness of breath [1].
- Harm to an unborn baby: do not become pregnant during treatment and for months afterwards [1].
For physicians
Boxed warning: the FDA label warns about three serious risks: hepatotoxicity, cardiac toxicity and embryo-fetal toxicity [1].
- Hepatotoxicity: mostly transient, asymptomatic rises in liver enzymes, but serious liver injury, including liver failure and death, has also occurred (3 fatal cases among 1624 trial patients) [1]. Nodular regenerative hyperplasia of the liver (NRH), which can lead to portal hypertension, was reported in 5 of 1624 patients [1].
- Cardiac toxicity: Kadcyla can reduce LVEF; in the EMILIA trial, left ventricular dysfunction occurred in 1.8% of patients in the Kadcyla group [1].
- Embryo-fetal toxicity: both trastuzumab (the antibody component) and DM1 can harm a fetus [1].
- Haemorrhage: cerebral, respiratory and gastrointestinal bleeding, sometimes fatal, has been reported [1]. In KATHERINE, bleeding occurred in 29% of the Kadcyla group vs 10% of the trastuzumab group, and 0.4% was grade 3 or higher (including one fatal intracranial haemorrhage) [1].
- Thrombocytopenia: in KATHERINE it occurred in 29% of patients in the Kadcyla group, with 6% grade 3 or higher; it was more common in Asian patients (19% grade 3 or higher) [1].
- Pulmonary toxicity: interstitial lung disease and pneumonitis, sometimes leading to acute respiratory distress syndrome or death, have been reported; in KATHERINE, pneumonitis was reported in 1.1%, and radiation pneumonitis in 1.8% of patients who received adjuvant radiotherapy with Kadcyla [1].
- Peripheral neuropathy: in KATHERINE it occurred in 32% of the Kadcyla group vs 17% of the trastuzumab group, with 1.6% grade 3 or higher [1].
- Infusion reactions and extravasation: infusion reactions occurred in 1.6% of KATHERINE patients; leakage of the drug under the skin can cause redness, pain or swelling at the infusion site [1].
When should I call my doctor?
If you have any of the following symptoms, contact your doctor or treatment team straight away [1]:
- Signs of liver damage: nausea, vomiting, abdominal pain (especially in the upper right abdomen), yellowing of the skin or eyes, dark urine, itching all over the body or loss of appetite
- New or worsening shortness of breath, or a cough
- Swelling of the ankles or legs, palpitations, weight gain of more than 5 pounds (about 2.3 kg) in 24 hours, dizziness or loss of consciousness
- Unusual or prolonged bleeding (such as a long nosebleed, vomiting blood, or black or bloody stools)
- Redness, pain or swelling at the infusion site
- Pregnancy or a possible pregnancy
In severe cases, such as severe shortness of breath, severe bleeding or loss of consciousness, call your local emergency number.
Interactions, pregnancy and precautions
- Other medicines: antifungals (ketoconazole, itraconazole, voriconazole), the antibiotic clarithromycin and the HIV medicine ritonavir may raise the amount of this drug and are best not taken with it [1]. Blood thinners and antiplatelet medicines (such as aspirin and clopidogrel) should be used with caution and closer follow-up, because the risk of bleeding is higher [1].
- Pregnancy and contraception: pregnancy status is checked before starting; women who could become pregnant should use effective contraception during treatment and for 7 months after the last dose, and men whose partner could become pregnant for 4 months after the last dose [1].
- Breastfeeding: do not breastfeed during treatment and for 7 months after the last dose [1].
- Fertility: based on animal studies, Kadcyla may impair fertility in women and men, and it is not known whether this is reversible; if you are planning to have children, talk to your doctor before starting [1].
- Vaccines: the FDA label gives no specific advice about vaccination; talk to your treatment team before any vaccine.
- Missed appointment: contact the treatment centre as soon as possible rather than waiting for the next cycle; the schedule is adjusted to keep 3 weeks between doses [1].
Frequently asked questions
How is Kadcyla different from Herceptin?
Kadcyla is the antibody trastuzumab with a cell-killing drug (DM1) attached; so its dose, side effects and administration are different, and the FDA label forbids substituting one drug for the other [1].
Is Kadcyla chemotherapy?
How long does treatment with Kadcyla last?
Why is a blood test needed before each infusion?
Because Kadcyla can damage the liver and lower platelets; the FDA label recommends checking liver enzymes, bilirubin and the platelet count before each dose, so that the dose can be lowered or treatment delayed if needed [1].
Has a newer drug replaced Kadcyla?
In a large study of high-risk patients with residual invasive disease after treatment before surgery, trastuzumab deruxtecan roughly halved recurrence compared with Kadcyla [4] and is now FDA-approved for this setting [5]. Even so, the choice of drug depends on each patient's situation (including the risk of lung side effects) and should be decided with the treating doctor.
Scientific evidence
Show detailsHide
Key studies
3 itemsTrastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer
Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer
Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer
Related cancer types
Treatment regimens (physicians)
References
6 referencesShow all references, 4 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1KADCYLA (ado-trastuzumab emtansine) for injection, for intravenous use: Prescribing Information
- 2
- 3Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer
- 4Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer
- 5
- 6
This page is based on reputable scientific sources and was last updated on 28 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
Printed from the website; the full and up-to-date version: https://drdabiri.com/en/drugs/trastuzumab-emtansine/