An antibody drug conjugate links an antibody that finds cancer cells to a powerful chemotherapy drug, delivering it inside the tumor. ADCs are now standard in HER2-positive, HER2-low and triple-negative breast cancer and in advanced bladder cancer, where enfortumab vedotin with pembrolizumab raised median survival from 16.1 to 31.5 months.
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Medical Oncology
An antibody finds the cancer cell and a chemotherapy payload rides along. In advanced bladder cancer, one combination nearly doubled median survival.
An antibody drug conjugate, or ADC, joins an antibody that recognizes a protein on the surface of cancer cells to a powerful chemotherapy drug by a chemical link. The antibody carries the drug to the tumor, the cell swallows the package, and the drug is released inside. ADCs have become standard in several breast cancers, bladder cancer, some lymphomas and ovarian cancer. In the EV-302 trial, enfortumab vedotin with pembrolizumab gave a median survival of 31.5 months against 16.1 with chemotherapy in untreated advanced bladder cancer, and in HER2-low breast cancer trastuzumab deruxtecan lengthened survival from 16.8 to 23.4 months.
31.5 vs 16.1 mo
Median survival in advanced bladder cancer, NEJM 2024
88.3% vs 77.0%
Free of invasive disease at 3 years, HER2-positive breast cancer after surgery, NEJM 2019
12.1 vs 6.7 mo
Median survival in triple-negative breast cancer, NEJM 2021
Free
Oncologist review of your pathology and scans
Free consultation
Send the pathology report with the receptor or target results, such as HER2 with its exact score, the latest CT or PET-CT, and a list of every treatment given so far with dates and the reason each one stopped. A medical oncologist tells you whether an ADC is approved for your cancer at this point in its course, which one, and what it asks of you. The opinion is free and places no obligation on you.
Doctors say antibody drug conjugate, and many simply say ADC, so the title of this page, Antibody Drug Conjugate Therapy - ADC Therapy, uses both. The idea dates from the 1980s. Only in the past decade have the links grown stable enough and the payloads strong enough to make it work, and the list of approved drugs now grows every year.
How an ADC works
Three parts in one molecule
1
The antibody
A laboratory-made antibody recognizes one protein that is plentiful on the cancer cell and scarce on normal cells, for example HER2, TROP2 or Nectin-4.
2
The linker
A chemical bridge holds the drug to the antibody in the bloodstream and breaks once the package is inside the cell. A stable linker keeps the drug away from healthy tissue on the way.
3
The payload
A chemotherapy drug far too toxic to give on its own, such as a topoisomerase inhibitor or a drug that blocks cell division. Some payloads also leak into neighboring cancer cells that carry little of the target, which helps in tumors with uneven expression.
Why it is not a gentle treatment
The antibody narrows the aim. It does not make the payload harmless. Some of the drug reaches healthy cells, and ADCs cause many of the effects of chemotherapy, including tiredness, nausea and, with some of them, hair loss, along with side effects of their own that depend on the target and the payload.
The target decides everything
No target, no benefit.
HER2-low, a category created by a drug
Breast cancers used to be called HER2 positive or negative. Tumors that score 1+ or 2+ without gene amplification, once grouped as negative, are now called HER2-low, because trastuzumab deruxtecan works in them. About half of all breast cancers fall into this group, so an old pathology report that says HER2 negative may need a fresh look at the actual score.
Which test each ADC needs
Trastuzumab emtansine and trastuzumab deruxtecan need a HER2 score from the pathologist. Sacituzumab govitecan targets TROP2, which almost all triple-negative and hormone receptor positive breast cancers carry, so no target test is required. Enfortumab vedotin targets Nectin-4, present in nearly all bladder cancers, and again needs no test. Mirvetuximab soravtansine in ovarian cancer requires a folate receptor alpha test. Ask the pathology laboratory to report the exact score as a number.
Breast cancer, three trials
Breast cancer is where ADCs have changed practice most, in three separate groups of patients.
HER2-positive, residual disease after surgery, KATHERINE
In 1,486 women who still had cancer in the breast or lymph nodes after chemotherapy and trastuzumab before surgery, switching to trastuzumab emtansine for 14 cycles after surgery left 88.3 percent free of invasive disease at three years, against 77.0 percent with trastuzumab, a hazard ratio of 0.50. von Minckwitz and colleagues, New England Journal of Medicine, 2019.
HER2-positive, advanced, DESTINY-Breast03
In 524 patients previously treated with trastuzumab and a taxane, trastuzumab deruxtecan left 75.8 percent alive and free of progression at 12 months against 34.1 percent with trastuzumab emtansine, and the tumor shrank in 79.7 against 34.2 percent. Lung inflammation occurred in 10.5 against 1.9 percent, none of it fatal. Cortes and colleagues, New England Journal of Medicine, 2022.
HER2-low, advanced, DESTINY-Breast04
In 557 patients with HER2-low disease after one or two chemotherapy regimens, trastuzumab deruxtecan gave a median survival of 23.4 months against 16.8 with chemotherapy. Lung inflammation occurred in 12.1 percent, and 0.8 percent died of it. Modi and colleagues, New England Journal of Medicine, 2022.
Triple-negative, advanced, ASCENT
In 468 patients whose cancer had progressed after at least two regimens, sacituzumab govitecan gave a median survival of 12.1 months against 6.7 with chemotherapy, and the tumor shrank in 35 against 5 percent. Severe neutropenia occurred in 51 percent and severe diarrhea in 10. Bardia and colleagues, New England Journal of Medicine, 2021.
Bladder cancer
Median survival nearly doubled
In EV-302, 886 patients with untreated advanced or metastatic urothelial cancer received enfortumab vedotin with pembrolizumab, or platinum chemotherapy. Median survival was 31.5 against 16.1 months, a hazard ratio of 0.47, and time without progression was 12.5 against 6.3 months. Severe treatment-related side effects occurred in 55.9 against 69.5 percent. Powles and colleagues, New England Journal of Medicine, 2024.
That result ended three decades in which platinum chemotherapy was the first treatment for advanced bladder cancer. The combination is given on days one and eight of a three-week cycle for enfortumab vedotin, with pembrolizumab on day one, and continues as long as it helps.
Who is a candidate
The candidate has a cancer type and a stage in which an ADC has been approved on the strength of a randomized trial, a tumor that carries the target where a test is needed, and enough strength and organ function to receive chemotherapy. The line of treatment matters. Trastuzumab deruxtecan for HER2-low disease, for example, comes after chemotherapy in advanced disease, and trastuzumab emtansine after surgery is for residual disease only.
When extra care is needed
Lung disease such as fibrosis or previous pneumonitis raises the risk of lung inflammation with trastuzumab deruxtecan. Existing nerve damage worsens with enfortumab vedotin, which also raises blood sugar in diabetes. Low baseline blood counts, liver disease and a weak heart with the HER2 drugs each change the plan. None of these is always a bar.
Approved ADCs at a glance
Seven ADCs see routine use.
This table scrolls sideways on a narrow screen. Swipe or drag to see every column.
Antibody drug conjugates in routine use
Drug
Target
Main use
Trastuzumab emtansine
HER2
HER2-positive breast cancer, residual disease after surgery and advanced disease
Trastuzumab deruxtecan
HER2
HER2-positive and HER2-low breast cancer, HER2-altered stomach and lung cancer
Sacituzumab govitecan
TROP2
Triple-negative and pretreated hormone receptor positive breast cancer
Enfortumab vedotin
Nectin-4
Advanced bladder cancer, with pembrolizumab
Brentuximab vedotin
CD30
Hodgkin lymphoma and some T-cell lymphomas
Polatuzumab vedotin
CD79b
Diffuse large B-cell lymphoma
Mirvetuximab soravtansine
Folate receptor alpha
Platinum-resistant ovarian cancer with a positive test
Approvals differ between countries
The list above reflects approvals in Europe and the United States. Availability and reimbursement vary. New indications arrive every year, so the oncologist checks the current position for your cancer, your stage and your country before recommending any of these drugs.
Side effects
Side effects follow the payload and the target. Two ADCs can feel completely different to the patient taking them.
Lung inflammation, the one to watch with trastuzumab deruxtecan
Interstitial lung disease occurred in 10.5 to 12.1 percent of patients in the two DESTINY-Breast trials. Caught early, when it shows only on a scan, it settles with a pause and steroids. Missed, it can be fatal, which is why a new cough or breathlessness means stopping the drug and calling the team the same day.
Each ADC has its own profile. Trastuzumab deruxtecan causes nausea, tiredness and hair loss. Sacituzumab govitecan lowers white cells and causes diarrhea and hair loss. Enfortumab vedotin causes rash, which can be severe in the first cycles, numbness in hands and feet, dry eyes and high blood sugar. Trastuzumab emtansine lowers platelets and raises liver tests. Mirvetuximab soravtansine affects the surface of the eye, and eye drops and checks by an eye doctor come with it.
A course of treatment, and the trip
What a treatment day looks like
From arrival to going home
Blood tests in the morning, a doctor's review, anti-sickness medicine, then the infusion in a day-treatment chair. The first infusion takes 60 to 90 minutes, later ones 30. Trastuzumab deruxtecan and trastuzumab emtansine are given every three weeks. Sacituzumab govitecan and enfortumab vedotin are given on days one and eight of a three-week cycle. A short observation follows, and the patient goes back to the hotel the same day.
Length of stay, the first visit and later cycles
A first stay of seven to ten days lets the team complete any missing test, give the first dose and see the patient again before the flight, since nausea and the first drop in blood counts arrive within that time. Later cycles follow the drug's schedule. A patient on a three-weekly drug can return for each cycle or continue with an oncologist at home using the written plan, while a day one and day eight schedule suits continuation at home better.
Cost, and what the office arranges
ADCs are among the costliest cancer drugs, and the price is set by the drug and the dose, which depends on body weight. The number of cycles depends on the response. Blood tests, scans, anti-sickness medicine, eye checks where required, and the treatment of any side effect add to it. Published packages in Istanbul cover the consultation, tests, the infusion day, an interpreter and transfers, and exclude the hotel, flights and the drug itself in some programs, so ask which applies. The oncologist's review of your reports, which comes first, is free. The coordinator writes in English, Arabic, French, Russian, Serbian, Romanian or Spanish, or arranges an interpreter, sends the appointment confirmation with an invitation letter naming the hospital and the treating doctor ten days before each visit, and books the hotel and transfers. Two family members may attend consultations, meals come in halal, vegetarian and diabetic versions, a prayer room is on site, and a female doctor can be requested at first contact.
Flying
You can fly the day after an infusion if you feel well and the blood counts allow. Carry anti-sickness and anti-diarrhea tablets in hand luggage. Avoid a flight in the week the white cells are expected to be lowest, which the team names in advance.
Monitoring between and after infusions
Every ADC dose starts with a blood test and a conversation. The table lists the checks that run alongside treatment, some before each dose and some every few months, and the reason for each, so that a doctor at home who has never given the drug can follow the same schedule, recognize a problem early and know when to call Istanbul.
This table scrolls sideways on a narrow screen. Swipe or drag to see every column.
What is checked, and how often
Check
How often
Why
Blood counts and liver tests
Before every dose
Neutropenia, low platelets, liver changes
Symptoms review
Before every dose
Cough, breathlessness, rash, numbness, diarrhea
Heart ultrasound
Every three months on HER2 drugs
Heart pumping strength
CT scan of the chest
Every two to three months
Response, and early signs of lung inflammation
Eye examination
Regularly on mirvetuximab, as needed on enfortumab
Surface of the eye
Call the team the same day
For a new cough, breathlessness or chest pain, a temperature of 38 degrees or higher, diarrhea of more than four stools above your normal, a spreading or blistering rash, or blurred vision. Once you are back home the coordinator remains reachable on the same WhatsApp number and passes clinical questions to the treating oncologist, and the written plan tells your local doctor what each warning sign means for this drug.
Antibody Drug Conjugate Therapy - ADC Therapy FAQ
What is an antibody drug conjugate?
It is a treatment that joins an antibody, which recognizes a single protein on the surface of cancer cells, to a strong chemotherapy drug by a chemical link. The antibody carries the drug to the tumor, where it is released inside the cell.
Is ADC therapy the same as chemotherapy?
It delivers a chemotherapy drug, so it shares some chemotherapy side effects, including tiredness, nausea and, with some ADCs, hair loss. The antibody concentrates the drug in the tumor, which is why the drugs work in situations where ordinary chemotherapy has failed.
Which cancers are treated with ADCs?
Breast cancer, both HER2-positive and HER2-low, triple-negative breast cancer, advanced bladder cancer, Hodgkin and some other lymphomas, ovarian cancer with a positive folate receptor test, and some stomach and lung cancers with HER2 changes.
How well do ADCs work?
In advanced bladder cancer, enfortumab vedotin with pembrolizumab gave a median survival of 31.5 months against 16.1 with chemotherapy. In HER2-low breast cancer, trastuzumab deruxtecan gave 23.4 against 16.8 months. Results differ by drug and cancer.
What is the most serious side effect?
It depends on the drug. With trastuzumab deruxtecan it is lung inflammation, seen in about one patient in ten in the trials, which is why any new cough or breathlessness must be reported the same day.
How often is an ADC given, and can I continue at home?
Every three weeks for the HER2 drugs, and on days one and eight of a three-week cycle for sacituzumab govitecan and enfortumab vedotin. After a first visit of seven to ten days, treatment can continue in Istanbul or with an oncologist at home following the written plan.
References
von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019;380(7):617-628.
Cortes J, Kim SB, Chung WP, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022;386(12):1143-1154.
Modi S, Jacot W, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022;387(1):9-20.
Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021;384(16):1529-1541.
Powles T, Valderrama BP, Gupta S, et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med. 2024;390(10):875-888.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Prof. Dr. Mustafa Teoman YANMAZ, Medical Oncology.
