Key points
- Trastuzumab deruxtecan (Enhertu) is an anti-HER2 antibody that carries a strong anticancer drug straight into the cancer cell [1] (read more).
- It is used in HER2-positive and even HER2-low breast cancer, and in some lung, stomach and other cancers with HER2 [1].
- The most important risk is lung damage (about 1 in 10 people); report a new cough, shortness of breath or fever straight away [1].
- It causes a lot of nausea; an anti-sickness medicine is given before every infusion [1].
- In HER2-positive breast cancer that had spread, this drug controlled the disease much longer than the previous drug (Kadcyla) [1, 2].
What is this drug and how does it work?
For physicians
Trastuzumab deruxtecan (in the United States fam-trastuzumab deruxtecan-nxki; abbreviated T-DXd), brand name Enhertu, is an antibody-drug conjugate (ADC) made of three parts: a humanised anti-HER2 monoclonal antibody, a cleavable linker, and the drug DXd, a topoisomerase I inhibitor [1]. Each antibody molecule carries approximately 8 deruxtecan molecules [1].
After the drug binds to HER2 on the tumour cell, the whole molecule enters the cell and lysosomal enzymes cleave the linker [1]. The released DXd, which crosses cell membranes, damages DNA and causes cell death [1]. In this way the drug acts as a "targeted carrier" that delivers the anticancer drug to cells that have HER2.
Enhertu must not be substituted for trastuzumab (Herceptin) or trastuzumab emtansine (Kadcyla) [1].
Which cancers is it used for?
According to the FDA label, trastuzumab deruxtecan is approved for adults with several cancers, including breast cancer, lung cancer and stomach cancer, and patients are selected on the basis of HER2 testing (HER2 protein expression, gene amplification or, in lung cancer, an HER2 mutation in tissue or blood) [1]. Approved uses may differ between countries, and not every patient with these cancers is a candidate for this drug.
Your doctor may prescribe this drug for:
- Early HER2-positive breast cancer — before surgery [1]
- Early HER2-positive breast cancer — after surgery [1, 3]
- HER2-positive breast cancer that has spread — first line [1, 4]
- HER2-positive breast cancer that has spread — after anti-HER2 treatment [1, 2]
- HER2-low or HER2-ultralow breast cancer (hormone receptor-positive) — that has spread [1, 5]
- HER2-low breast cancer — that has spread [1, 6]
- Non-small cell lung cancer with an HER2 mutation [1]
- HER2-positive cancer of the stomach or the junction between the stomach and oesophagus [1, 7, 8]
- HER2-positive solid tumours (IHC 3+) [1, 9]
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 |
|---|---|---|
| Early HER2-positive breast cancer — before surgery | Stage II or III; 4 cycles of Enhertu, then 4 cycles of THP (taxane, trastuzumab and pertuzumab) [1] | DESTINY-Breast11: pathological complete response 67.3% vs 56.3% with ddAC followed by THP [1] |
| Early HER2-positive breast cancer — after surgery | Residual invasive disease after neoadjuvant treatment with trastuzumab (with or without pertuzumab) and a taxane; 14 cycles [1] | DESTINY-Breast05 [3]: 3-year invasive disease-free survival 92.4% vs 83.7% with trastuzumab emtansine (HR 0.47) [1] |
| HER2-positive metastatic breast cancer — first line | With pertuzumab, in unresectable or metastatic disease [1] | DESTINY-Breast09 [4]: median progression-free survival 40.7 vs 26.9 months with THP (HR 0.56) [1] |
| HER2-positive metastatic breast cancer — after anti-HER2 treatment | Single agent, after one anti-HER2 regimen in the metastatic setting, or recurrence during or within 6 months of treatment for early disease [1] | DESTINY-Breast03 [2]: vs trastuzumab emtansine, HR for progression-free survival 0.28 and HR for overall survival 0.64 [1] |
| HER2-low or HER2-ultralow (hormone receptor-positive) breast cancer — metastatic | HER2-low (IHC 1+ or IHC 2+ with negative ISH) or HER2-ultralow (IHC 0 with membrane staining), after progression on one or more endocrine therapies in the metastatic setting [1] | DESTINY-Breast06 [5]: median progression-free survival 13.2 vs 8.1 months with chemotherapy [1] |
| HER2-low breast cancer — metastatic | After one chemotherapy in the metastatic setting, or recurrence during or within 6 months of adjuvant chemotherapy [1] | DESTINY-Breast04 [6]: in the hormone receptor-positive group, median progression-free survival 10.1 vs 5.4 months and median overall survival 23.9 vs 17.5 months with chemotherapy [1] |
| Non-small cell lung cancer with an HER2 mutation | Unresectable or metastatic, with an activating HER2 (ERBB2) mutation, after one previous systemic treatment; accelerated approval [1] | DESTINY-Lung02: confirmed objective response 50.0% and median duration of response 12.6 months [1] |
| HER2-positive gastric or gastro-oesophageal junction cancer | Locally advanced or metastatic, after a trastuzumab-based regimen [1] | DESTINY-Gastric01 [7]: median overall survival 12.5 vs 8.4 months with irinotecan or paclitaxel [1]; DESTINY-Gastric04: median overall survival 14.7 vs 11.4 months vs ramucirumab + paclitaxel [8] |
| HER2-positive solid tumours (IHC 3+) | Unresectable or metastatic, after previous systemic treatment and with no satisfactory alternative; accelerated approval [1] | DESTINY-PanTumor02 [9], DESTINY-Lung01 and DESTINY-CRC02: confirmed objective response 51.4%, 52.9% and 46.9% respectively [1] |
THP: taxane + trastuzumab + pertuzumab. "Accelerated approval" means continued approval depends on proof of clinical benefit in a confirmatory trial.
How it is given and dose
Treatment regimens and doses: index5 regimens
Enhertu is given as an intravenous infusion (drip) at the treatment centre once every 3 weeks (a 21-day cycle) [1]. The first infusion is given over 90 minutes and later infusions, if well tolerated, over 30 minutes [1]. Medicines to prevent nausea and vomiting are given before each infusion [1].
- Length of treatment: before surgery in early breast cancer, 4 cycles of Enhertu and then 4 cycles of THP; after surgery, 14 cycles; in metastatic disease, until the disease progresses or side effects become unacceptable [1].
- Before starting: an HER2 test (or an HER2 mutation test in lung cancer), a full blood count, a measurement of heart function (LVEF) and, in women who could become pregnant, a pregnancy test [1].
- During treatment: blood counts before each dose, regular heart checks when needed, and attention to any new breathing symptom [1].
Before starting: HER2 (IHC/ISH) or ERBB2 mutation (in lung; if negative in plasma, test tumour tissue); CBC; LVEF (not studied with LVEF below 50%); pregnancy test [1].
Administration: do not substitute with trastuzumab or trastuzumab emtansine (check the vial label). Highly emetogenic (including delayed nausea): antiemetic prophylaxis before each dose. Dilute only in 100 mL of 5% dextrose (sodium chloride must not be used); protect the bag from light; polyolefin or polybutadiene set with a 0.2 or 0.22 micron PES or PS filter; not as a push or bolus [1].
ILD/pneumonitis (boxed warning): investigate any new respiratory symptom (cough, dyspnoea, fever) promptly with imaging [1].
- Grade 1 ILD/pneumonitis (asymptomatic): hold until recovery to grade 0; if resolved within 28 days of onset: same dose; after more than 28 days: one level lower; consider corticosteroids (e.g. prednisolone 0.5 mg/kg/day or more). Grade 2 or higher: stop permanently and promptly start corticosteroids (e.g. prednisolone 1 mg/kg/day or more) for at least 14 days, then taper over at least 4 weeks.
For physicians
Dose and schedule (FDA label)
Single agent 5.4 mg/kg
HER2-positive, HER2-low or HER2-ultralow metastatic breast cancer; NSCLC with an HER2 mutation; HER2-positive solid tumours (IHC 3+)Cycle length: Every 3 weeks
HER2-positive, HER2-low or HER2-ultralow metastatic breast cancer; NSCLC with an HER2 mutation; HER2-positive solid tumours (IHC 3+)
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab deruxtecan (Enhertu) | 5.4 mg/kg | IV infusion; initial 90 minutes, then 30 minutes if tolerated | Day 1 |
[1]
Gastric or GEJ cancer — 6.4 mg/kg
HER2-positive (IHC 3+ or IHC 2+/ISH+) locally advanced or metastatic disease after a trastuzumab-containing regimenCycle length: Every 3 weeks
HER2-positive (IHC 3+ or IHC 2+/ISH+) locally advanced or metastatic disease after a trastuzumab-containing regimen
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab deruxtecan (Enhertu) | 6.4 mg/kg | IV infusion; initial 90 minutes, then 30 minutes if tolerated | Day 1 |
If possible, reassess HER2 on a new sample after trastuzumab treatment [1].
With pertuzumab (DESTINY-Breast09)
HER2-positive metastatic or unresectable breast cancer, first lineCycle length: Every 3 weeks
HER2-positive metastatic or unresectable breast cancer, first line
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab deruxtecan (Enhertu) | 5.4 mg/kg | IV infusion; initial 90 minutes, then 30 minutes if tolerated | Day 1 |
| Pertuzumab | Cycle 1: 840 mg; then 420 mg | IV, 30 minutes after Enhertu | Day 1 |
Pertuzumab must not be given alone [1].
Evidence: DESTINY-Breast09 (2026)
Before surgery: Enhertu then THP (DESTINY-Breast11)
Early HER2-positive breast cancer (stage II or III)Cycle length: Every 3 weeks
Early HER2-positive breast cancer (stage II or III)
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| First 4 cycles | |||
| Trastuzumab deruxtecan (Enhertu) | 5.4 mg/kg | IV infusion; initial 90 minutes, then 30 minutes if tolerated | Day 1 |
| Next 4 cycles | |||
| Taxane + trastuzumab + pertuzumab (THP) | Trastuzumab 6 mg/kg; pertuzumab 840 then 420 mg | IV | Every 3 weeks |
[1]
After surgery with residual disease (DESTINY-Breast05)
HER2-positive breast cancer with residual invasive disease after neoadjuvant trastuzumab (± pertuzumab) and a taxaneCycle length: Every 3 weeks
HER2-positive breast cancer with residual invasive disease after neoadjuvant trastuzumab (± pertuzumab) and a taxane
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Trastuzumab deruxtecan (Enhertu) | 5.4 mg/kg | IV infusion; initial 90 minutes, then 30 minutes if tolerated | Day 1 |
In the adjuvant setting, when ILD is suspected, rule out radiation pneumonitis; if only radiation pneumonitis is likely, consider holding for grade 2 and stop permanently for grade 3 or higher [1].
Evidence: DESTINY-Breast05 (2026)
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 reaction: slow or interrupt; severe reaction: stop permanently [1].
Delayed or missed dose: give as soon as possible and keep a 3-week interval from then on, at the dose and rate last tolerated [1].
Dose levels: 5.4 → 4.4 → 3.2 mg/kg (gastric: 6.4 → 5.4 → 4.4); if a further reduction is needed: stop; do not re-escalate after a reduction [1].
Dose adjustment for other toxicities [1]:
- Grade 3 neutropenia: hold until grade 2 or less, same dose; grade 4: hold until grade 2 or less and one level lower. Febrile neutropenia: hold until resolved and one level lower.
- Grade 3 thrombocytopenia: hold until grade 1 or less, same dose; grade 4: hold until grade 1 or less and one level lower.
- LVEF above 45% with a fall of 10 to 20%: continue. LVEF 40 to 45% with a fall of less than 10%: continue and repeat within 3 weeks; with a fall of 10 to 20%: hold and repeat within 3 weeks (if it does not recover to within 10% of baseline, stop permanently; if it recovers, continue at the same dose). LVEF below 40% or a fall of more than 20% (confirmed within 3 weeks) or symptomatic heart failure: stop permanently.
Kidney and liver: CLcr 30 to less than 90 mL/min: no adjustment (with moderate impairment, grade 1 and 2 ILD was more common; monitor more often). Mild or moderate hepatic impairment: no adjustment (monitor for toxicity in moderate impairment). No dose has been established in severe renal or hepatic impairment [1].
Monitoring: CBC before each dose; LVEF regularly [1].
Side effects
The most common side effects:
For physicians
In a pooled group of 2233 patients who received single-agent Enhertu at 5.4 mg/kg in ten trials, the most common side effects (20% or more, including laboratory findings) were [1]:
- Low white blood cells 73%, low haemoglobin 67%, low neutrophils 65%, low lymphocytes 60% and low platelets 48%
- Nausea 72%, vomiting 38%, constipation 32%, decreased appetite 31% and diarrhoea 30%
- Fatigue 55% and musculoskeletal pain 24%
- Raised liver enzymes AST 46% and ALT 43%, raised alkaline phosphatase 39% and low blood potassium 32%
- Hair loss 37%
In 431 patients who received Enhertu with pertuzumab, some side effects were more common, including nausea 74%, diarrhoea 64%, fatigue 53%, hair loss 48%, vomiting 46% and upper respiratory tract infection 32% [1]. In gastric cancer (6.4 mg/kg dose), low blood counts, nausea, decreased appetite, fatigue, diarrhoea, vomiting, constipation, fever and hair loss were also common [1].
Serious side effects
These side effects are less common but serious; if you notice any sign of them, tell your team early:
- Lung damage: the most important risk of this drug; in about 1 in 10 people, usually in the first to middle months of treatment. Report a new cough, shortness of breath or fever straight away; early diagnosis saves lives [1].
- Fever or chills, because your white blood cells may be low [1].
- A weakened heart: shortness of breath, swollen legs or palpitations; heart function is checked before and during treatment [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 two serious risks: interstitial lung disease and pneumonitis, and embryo-fetal toxicity [1].
- Interstitial lung disease (ILD) and pneumonitis: can be severe, life-threatening or fatal [1]. In patients receiving single-agent 5.4 mg/kg, ILD occurred in 12%, with a median time to onset of 5.5 months, and was fatal in 0.9% [1]. With pertuzumab, ILD also occurred in 12% of patients (fatal in 0.5%), in neoadjuvant treatment (DESTINY-Breast11) in 4.4%, and in gastric cancer at 6.4 mg/kg in 10% [1]. Mild to moderate ILD was seen more often in patients with moderate renal impairment [1].
- Neutropenia: at 5.4 mg/kg, neutropenia occurred in 65% of patients, grade 3 or 4 in 19%, and febrile neutropenia was reported in 1%; in gastric cancer (6.4 mg/kg) these figures were 72%, 51% and 4.8% [1].
- Left ventricular dysfunction: with single-agent 5.4 mg/kg in 4.6% of patients (grade 3 or 4 in 0.6%), and with pertuzumab, decreased LVEF was reported in 11% (grade 3 or 4 in 2.1%) [1].
- Embryo-fetal toxicity: both the anti-HER2 antibody component and DXd can harm a fetus; use of anti-HER2 antibodies in pregnancy has been associated with oligohydramnios and fatal pulmonary hypoplasia, skeletal abnormalities and neonatal death [1].
When should I call my doctor?
If you have any of the following symptoms, contact your doctor or treatment team straight away [1]:
- Cough, shortness of breath, fever or any new or worsening breathing symptom (such as chest tightness or wheezing)
- Fever or chills, or any sign of infection
- New or worsening shortness of breath or cough with tiredness, swollen ankles or legs, an irregular heartbeat, sudden weight gain, dizziness or loss of consciousness
- Pregnancy or a possible pregnancy
In severe cases, such as severe shortness of breath or loss of consciousness, call your local emergency number.
Interactions, pregnancy and precautions
- Other medicines: antifungal and HIV medicines hardly change the amount of this drug [1]. Even so, tell your treatment team about all your medicines, over-the-counter medicines, vitamins and herbal supplements [1].
- Pregnancy and contraception: a pregnancy test is done 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, Enhertu may impair male fertility; if you are concerned, 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 your doctor straight away to arrange a new appointment rather than waiting for the next cycle; the schedule is adjusted to keep 3 weeks between doses [1].
Frequently asked questions
Is Enhertu chemotherapy?
Enhertu is an antibody-drug conjugate: an anti-HER2 antibody that carries a cell-killing drug (a topoisomerase I inhibitor) and delivers it to cells that have HER2 [1]. So it is both a targeted treatment and partly works like chemotherapy; this is why it has side effects such as nausea, low blood counts and hair loss [1].
What does HER2-low mean, and am I a candidate for this drug?
"HER2-low" means the tumour sample test showed a small amount of HER2, but not enough for the tumour to count as "HER2-positive"; "HER2-ultralow" means only a few tumour cells have a little HER2 [1]. This status must be determined with an approved test, and the treatment decision also depends on your previous treatments [1].
Does Enhertu cause hair loss?
About 1 in every 3 patients on this drug, and nearly half of patients on this drug with pertuzumab, had hair loss [1].
Why do a cough or shortness of breath matter during treatment?
How is Enhertu different from Kadcyla (trastuzumab emtansine)?
Both are anti-HER2 antibody-drug conjugates, but the attached drug and their doses are different, and they must not be used in place of each other [1]. In two head-to-head studies, Enhertu gave better results than trastuzumab emtansine in metastatic HER2-positive breast cancer (DESTINY-Breast03) [2] and in residual disease after treatment before surgery (DESTINY-Breast05) [3].
Scientific evidence
Show detailsHide
Key studies
7 itemsTrastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer
Trastuzumab Deruxtecan in Residual HER2-Positive Early Breast Cancer
Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer
Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer
Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer
Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial
Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer
Related cancer types
Treatment regimens (physicians)
References
9 referencesShow all references, 8 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.
- 1ENHERTU (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use: Prescribing Information
- 2
- 3
- 4Trastuzumab Deruxtecan plus Pertuzumab for HER2-Positive Metastatic Breast Cancer
- 5Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer
- 6Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer
- 7Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer
- 8Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer
- 9Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial
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-deruxtecan/