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
Medical Oncology
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.
75.8% vs 34.1%
Cancer held in check at one year, against T-DM1, DESTINY-Breast03
23.4 vs 16.8 mo
Median survival in HER2-low breast cancer, against chemotherapy, DESTINY-Breast04
51% vs 14%
Tumor shrinkage in HER2-positive stomach cancer, DESTINY-Gastric01
Free
Review of your HER2 result and treatment history
Free consultation
The review of your file is free and commits you to nothing. Send the pathology report with the HER2 score and the method used, the hormone receptor result, the most recent scans with a chest CT, every treatment given so far with dates, and any history of lung disease. A medical oncologist tells you whether trastuzumab deruxtecan fits your cancer at this point, what dose and schedule, and how the lung checks will be arranged near home, and a coordinator answers in your own language.
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
Trastuzumab, the same antibody used against HER2 for more than twenty years. It carries the payload to any cell with HER2 on its surface and is taken inside when it binds.
The linker
A chemical bridge that stays intact in the bloodstream and is cut by enzymes inside the cancer cell. That keeps most of the chemotherapy away from healthy tissue until it arrives.
The payload
Deruxtecan, a topoisomerase I inhibitor, a class of chemotherapy that breaks DNA as cells divide. Each antibody carries eight molecules of it, more than earlier drugs of this type carried.
Why it reaches cells with little HER2
Once released, deruxtecan crosses cell membranes and kills neighboring cancer cells, whether or not they carry HER2 themselves. Doctors call this the bystander effect. It is why the drug works in HER2-low cancer, where trastuzumab alone does nothing, and why a cancer made of cells with patchy HER2 still responds.
Who receives it
On a narrow screen, slide the table sideways to reach every column.
Where trastuzumab deruxtecan is used
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.
The numbers
Alive without the cancer growing at one year, 75.8 percent against 34.1 percent. Tumors shrank in 79.7 percent of patients on trastuzumab deruxtecan and in 34.2 percent on T-DM1, and 94.1 percent against 85.9 percent were alive at one year. Serious drug-related side effects in 45.1 percent against 39.8 percent. Drug-related lung inflammation in 10.5 percent against 1.9 percent, with no case of the two most severe grades.
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
A group with no HER2 drug until 2022
Around half of breast cancers labeled HER2-negative carry a small amount of HER2, scored IHC 1+ or IHC 2+ with a negative FISH. Trastuzumab does nothing for them. Trastuzumab deruxtecan, through the bystander effect, does.
On a narrow screen, slide the table sideways to reach every column.
DESTINY-Breast04, New England Journal of Medicine 2022
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
187 patients with HER2-positive stomach or gastroesophageal junction cancer that had progressed after at least two treatments including trastuzumab, in Japan and South Korea. Tumor shrinkage in 51 percent against 14 percent with chemotherapy. Median survival 12.5 months against 8.4. Published in the New England Journal of Medicine in 2020.
The price
A drop in white blood cells to a serious level in 51 percent, anemia in 38 percent, and lung inflammation in 12 of the 125 patients treated, three of them severe. The dose for stomach cancer is higher than for breast cancer, and the blood count is watched closely for that reason.
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
A chest CT, a measurement of oxygen saturation, kidney function, and a record of any lung disease or earlier chest radiation.
During treatment
A chest CT every six to twelve weeks, and an oxygen reading at every visit. The patient checks for a new cough, breathlessness or fever every day and reports any of them the same day.
Grade 1, changes on the scan without symptoms
The drug is paused and steroids are started. When the scan clears, it can restart, at the same dose if the changes resolved within four weeks.
Grade 2 or higher, symptoms
The drug stops for good. Steroids follow at a higher dose, with oxygen when the saturation falls and admission to hospital for the more severe grades, where a lung specialist joins the care.
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
Common, building over the first cycles. Rest and gentle activity both help.
Hair thinning
Many patients notice it. Complete hair loss is less common.
Low blood counts
White cells, red cells and platelets fall in some patients, more at the dose used for stomach cancer. A blood count before every cycle decides whether it goes ahead.
The heart
Trastuzumab deruxtecan can weaken the pumping of the heart, as trastuzumab does, and a heart scan is repeated at intervals.
The infusion
Dose and schedule
5.4 milligrams per kilogram every three weeks for breast cancer, 6.4 for stomach cancer, given into a vein. Treatment continues for as long as it works and is tolerated.
How long it takes
Ninety minutes for the first infusion, and thirty for later ones when the first went smoothly. Blood tests and a visit with the oncologist come first, so allow half a day.
Nothing about the infusion itself is difficult. The rules around it are what matter.
On the same site
Biruni Hospital gives the drug in its oncology day unit, with the chest CT, the blood tests and the heart scan on the same site. Breast surgery, radiotherapy on an Elekta Versa HD linear accelerator and a pulmonology team for any lung problem are in the same building.
Days in Istanbul
The length of stay turns on one decision, whether the first cycle alone is given here or several.
Starting treatment
Four to five days. Consultation, chest CT and blood tests on the first two days, the first infusion on the third, and a day or two to watch for nausea before flying.
Later cycles
Every three weeks, by an oncologist near home on the protocol we write, or here for patients who prefer to return.
Flying
The infusion sets no limit on flying. Carry the anti-sickness tablets in hand luggage, and do not fly with a new cough, breathlessness or fever until a doctor has seen you.
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
Priced per vial and dosed by body weight, so a heavier patient needs more vials each cycle. It is the largest line by a wide margin.
Everything else
The consultation, the chest CT, the heart scan, the blood tests and the anti-sickness medicines, each a separate and much smaller line.
Before you compare
No figure appears on this page. Packages published by Turkish hospitals and medical travel agencies for targeted cancer drugs cover the consultation, the drug for a stated number of cycles and the infusion day, and leave out later cycles, the monitoring scans, flights and accommodation. A quote you can compare states your weight, the number of vials per cycle, the number of cycles and whether the chest CT is inside the figure. It follows the free review.
Coordinator, language, companion
Four things are arranged for every international patient, whatever the treatment.
1
One coordinator
Biruni Hospital assigns one coordinator from the first message, reachable on the same WhatsApp number afterwards, who also relays scans and results from home.
2
Language
The international patients team works in English, Arabic, French, Russian, Serbian, Romanian and Spanish and arranges interpreters for other languages. The interpreter sits in on the first consultation, where the lung warning signs are explained.
3
Travel and paperwork
Accommodation close to the hospital, airport transfers, the car to each visit, and an appointment confirmation and invitation letter for a visa ten days or so before travel.
4
Daily needs
Halal, vegetarian and diabetic meals, a prayer room on site, and a female physician where the rota allows for anyone who asks in the first message.
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.
On a narrow screen, slide the table sideways to reach every column.
Checks while on trastuzumab deruxtecan
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.
Enhertu is the brand name of trastuzumab deruxtecan, an antibody-drug conjugate. The antibody trastuzumab finds cancer cells with HER2 and delivers a chemotherapy drug, deruxtecan, inside them.
Who is trastuzumab deruxtecan for?
Metastatic HER2-positive breast cancer after a first HER2 treatment, metastatic HER2-low breast cancer after chemotherapy, HER2-positive stomach cancer after trastuzumab, HER2-mutant lung cancer, and in some countries other HER2 3+ tumors.
How well does it work?
In DESTINY-Breast03, 75.8 percent of patients were free of progression at one year against 34.1 percent on T-DM1. In HER2-low breast cancer, median survival was 23.4 months against 16.8 months on chemotherapy.
What is the lung risk?
Drug-related lung inflammation occurred in 15.4 percent of 1,150 patients across nine trials, mostly mild and mostly in the first year. It is caught early with regular chest CT scans and treated with steroids.
How often is it given?
Every three weeks by infusion into a vein, thirty to ninety minutes, for as long as it works and is tolerated.
How long do I need to stay in Istanbul?
Four to five days to start. Later cycles are given near home on our protocol, with scans sent back for review.
Will the staff be able to speak my language?
The international patients team works in English, Arabic, French, Russian, Serbian, Romanian and Spanish and arranges interpreters for other languages.
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.
