Antibody Drug Conjugate Therapy - ADC Therapy
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.
About This Department
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.
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
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 drugBreast 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
Breast cancer, three trials
HER2-positive, residual disease after surgery, KATHERINE
HER2-positive, advanced, DESTINY-Breast03
HER2-low, advanced, DESTINY-Breast04
Triple-negative, advanced, ASCENT
Bladder cancer
Median survival nearly doubledIn 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.
Who is a candidate
When extra care is needed
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.
| 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 countriesThe 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 deruxtecanInterstitial 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.
A course of treatment, and the trip
What a treatment day looks like
From arrival to going home
Length of stay, the first visit and later cycles
Cost, and what the office arranges
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.
| 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
Antibody Drug Conjugate Therapy - ADC Therapy FAQ
What is an antibody drug conjugate?
Is ADC therapy the same as chemotherapy?
Which cancers are treated with ADCs?
How well do ADCs work?
What is the most serious side effect?
How often is an ADC given, and can I continue at home?
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. Metin GÜDEN, Radiation Oncology.
Medically reviewed by
Prof. Dr. Metin GÜDEN
Radiation Oncology
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