T-Dxd Therapy - Enhertu/Trastuzumab Deruxtecan
Trastuzumab deruxtecan, sold as Enhertu, is an antibody that carries chemotherapy into HER2 cancer cells and their neighbors. It held HER2-positive breast cancer in check at one year in 75.8 percent of patients against 34.1 percent on T-DM1, lengthened survival in HER2-low breast cancer, and needs regular lung checks.
About This Department
An antibody that carries chemotherapy to the cancer cell. Trastuzumab deruxtecan works even where HER2 is barely there.
Your oncologist has named Enhertu, trastuzumab deruxtecan, T-DXd for short, as the next treatment, or you have read that it may help a cancer other drugs have stopped controlling. It belongs to a family called antibody-drug conjugates. An antibody finds cancer cells carrying HER2 with a strong chemotherapy drug attached, and the two separate only inside the cell. Some of the released drug leaks next door. Cells with little HER2 of their own die too. Against the drug it replaced in HER2-positive breast cancer, it kept the disease in check at one year in 75.8 percent of patients against 34.1 percent. In HER2-low breast cancer, a group that until 2022 had no HER2 drug at all, median survival rose from 16.8 to 23.4 months. In stomach cancer that had outgrown trastuzumab, tumors shrank in half the patients. It also inflames the lungs in some patients, and that risk shapes how the drug is given and watched. This page covers who it suits, what the trials show, how the lungs are protected, and how three-weekly infusions fit with a visit to Istanbul.
How the drug is built
T-Dxd Therapy - Enhertu/Trastuzumab Deruxtecan uses a drug built in three parts, and each part explains something about how it behaves in the body.
The antibody
The linker
The payload
Who receives it
| Cancer | HER2 status | Stage of treatment |
|---|---|---|
| Breast | HER2-positive, IHC 3+ or IHC 2+ with a positive FISH | Metastatic disease after a first HER2 treatment. Increasingly earlier |
| Breast | HER2-low, IHC 1+ or IHC 2+ with a negative FISH | Metastatic disease after chemotherapy, and after hormone treatment when receptors are positive |
| Stomach and gastroesophageal junction | HER2-positive | Advanced disease after trastuzumab |
| Lung, non-small cell | HER2 mutation found on genetic testing | Advanced disease after earlier treatment |
| Other solid tumors | HER2 IHC 3+ | Advanced disease with no satisfactory alternative, in some countries |
Approvals differ between countries
Regulators have approved the drug for these uses at different times, and the list above does not apply everywhere in the same form. The review sets out what is available and reimbursed where you live, because a patient who starts the drug here continues it at home in nearly every case.
HER2-positive breast cancer
DESTINY-Breast03
The trial randomized 524 patients with metastatic HER2-positive breast cancer that had progressed after trastuzumab and a taxane, to trastuzumab deruxtecan or to trastuzumab emtansine, T-DM1, the standard second treatment at the time. The results were reported in the New England Journal of Medicine in 2022.
Those figures moved trastuzumab deruxtecan to the second line of treatment for HER2-positive metastatic breast cancer, straight after pertuzumab, trastuzumab and a taxane. It also reaches the brain, where HER2-positive breast cancer spreads more than most.
HER2-low breast cancer
| Measure | Trastuzumab deruxtecan | Chemotherapy chosen by the physician |
|---|---|---|
| Patients | 557 in all, after one or two earlier chemotherapy lines, 89 percent hormone receptor positive | Same trial, randomized 2 to 1 |
| Median time without progression, all patients | 9.9 months | 5.1 months |
| Median survival, all patients | 23.4 months | 16.8 months |
| Median survival, hormone receptor positive | 23.9 months | 17.5 months |
| Serious side effects | 52.6 percent | 67.4 percent |
| Drug-related lung inflammation | 12.1 percent, 0.8 percent fatal | Not reported for chemotherapy |
DESTINY-Breast04 created a new category. A HER2 score of 0 against 1+ used to make no difference to treatment, and now it does. A report that says only HER2-negative needs a second look for the exact score. Old slides are rescored.
Stomach cancer
DESTINY-Gastric01
The price
The trial was small by the standards of breast cancer and ran only in Japan and South Korea, where stomach cancer is common. Guidelines in Europe and North America have since adopted the drug as an option after trastuzumab, and the review says whether it is the right next step for you.
A stomach cancer that has outgrown trastuzumab is not the end of HER2 treatment. The HER2 status can change after the first line, so a new biopsy to confirm it is part of planning.
The lung risk
15.4 percent across nine trials and 1,150 patients. The rate of drug-related lung inflammation in the pooled analysis published in ESMO Open in 2022. Most cases were mild, 87 percent began within twelve months of the first dose, and 2.2 percent of all patients died of it.
Interstitial lung disease, or pneumonitis, is inflammation of the lung tissue itself. It shows as a dry cough, breathlessness, a low fever or a fall in the oxygen level, and it may appear on a CT scan before any symptom does. Caught early, it settles in nearly every case. Caught late, it scars the lungs, and in a small share of patients it kills.
The same analysis named the features linked to a higher risk. Age under 65, treatment in Japan, a dose above the standard, oxygen saturation below 95 percent at the start, moderate or severe kidney impairment, existing lung disease, and more than four years since the cancer was first diagnosed. None of these rules the drug out. Each one tightens the watch.
How the lungs are watched
Four rules, set by the manufacturer and followed by oncologists everywhere, decide what happens when the lungs change.
Before the first dose
During treatment
Grade 1, changes on the scan without symptoms
Grade 2 or higher, symptoms
A new cough on this drug means a phone call the same day. Waiting for the next cycle turns a mild problem into a dangerous one.
Other side effects
Nausea comes first. It is stronger than with most HER2 drugs, and two anti-sickness medicines before each dose, with a third for the days after, keep it manageable for nearly everyone.
Beyond the lungs, the side effects resemble those of chemotherapy, milder in some ways and stronger in others.
Tiredness
Hair thinning
Low blood counts
The heart
The infusion
Dose and schedule
How long it takes
Nothing about the infusion itself is difficult. The rules around it are what matter.
Days in Istanbul
The length of stay turns on one decision, whether the first cycle alone is given here or several.
Starting treatment
Later cycles
Flying
Infusions every three weeks for months cannot sensibly be given by air. Most patients take the first cycle here and the rest at home, sending every scan back to us for review by the oncologist who wrote the protocol.
What a quote contains
A quote for this drug has two parts, and one of them dwarfs the other.
The drug
Everything else
Coordinator, language, companion
Four things are arranged for every international patient, whatever the treatment.
Bring someone with you if you can. A companion hears the lung warning signs too, and is often the first to notice a new cough.
Between cycles, at home
Once you get back home, your oncologist receives the protocol, the dose, the anti-sickness plan, the rules for pausing and stopping, and the schedule below.
| Check | How often |
|---|---|
| Blood count and liver tests | Before every cycle |
| Oxygen saturation and questions about cough and breathing | At every visit |
| Chest CT | Every six to twelve weeks, and at once for any new chest symptom |
| Heart scan | At intervals set by the oncologist |
| Staging scans | Every two to three months |
Sending results
Every scan and blood result goes to the coordinator. The oncologist here reviews it at no charge. A new cough, breathlessness or fever goes to a local doctor the same day, with the protocol in hand, because steroids started early matter more than anything else on this page. Tell every doctor you see that you are taking trastuzumab deruxtecan, including the one in an emergency department who has never heard of it, and show them the letter we give you, which names the drug, the lung risk and the steroid dose to start.
T-Dxd Therapy - Enhertu/Trastuzumab Deruxtecan FAQ
What is Enhertu?
Who is trastuzumab deruxtecan for?
How well does it work?
What is the lung risk?
How often is it given?
How long do I need to stay in Istanbul?
Will the staff be able to speak my language?
References
- Cortés J, Kim SB, Chung WP, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. The New England Journal of Medicine. 2022;386(12):1143-1154.
- Modi S, Jacot W, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. The New England Journal of Medicine. 2022;387(1):9-20.
- Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. The New England Journal of Medicine. 2020;382(25):2419-2430.
- Powell CA, Modi S, Iwata H, et al. Pooled analysis of drug-related interstitial lung disease and/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies. ESMO Open. 2022;7(4):100554.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Prof. Dr. Mustafa Teoman YANMAZ, Medical Oncology.
Medically reviewed by
Prof. Dr. Mustafa Teoman YANMAZ
Medical Oncology
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