Antibody-Drug Conjugates (ADC)

What is it?

An antibody-drug conjugate is a drug in which a powerful chemotherapy molecule is attached by a chemical bridge to the tip of a monoclonal antibody. It is called an ADC for short. The aim is to bring the payload as close as possible to the cells that carry the target.

This does not mean that chemotherapy disappears altogether. The payload itself is a cytotoxic drug; the antibody tries to narrow down its address. Healthy tissues can still be affected. Which ADC is appropriate depends on the amount of the protein on the surface and on previous treatments.

How does it work?

The antibody attaches to the protein on the tumour surface. The cell takes the antibody in; when the bridge breaks, the payload is released and disrupts cell division. Trastuzumab deruxtecan and trastuzumab emtansine target the HER2 protein, enfortumab vedotin the nectin-4 protein and sacituzumab govitecan the Trop-2 protein.

A small amount of payload passing to neighbouring cells may also affect the surrounding tumour cells. This property can be beneficial with some drugs and also changes the side-effect profile.

In which cancers is it used?

HER2-positive and selected HER2-low breast cancer, some stomach cancers, urothelial bladder cancer and triple-negative breast cancer are examples where ADC regimens are discussed. The list varies according to drug approvals and the protein expression of the tumour.

Which treatment is appropriate is discussed at the tumour board, with the relevant specialties taking part, by considering the type, stage and molecular features of the cancer and the person’s general condition together. Which drugs have been used before influences the choice of ADC.

How is it given?

Treatment is given intravenously, usually every three weeks. The first doses are monitored more closely for infusion reactions. The blood count is checked before each course. Nausea prophylaxis is planned according to the drug payload.

Lung symptoms are asked about specifically in those using trastuzumab deruxtecan. Changes in vision have been reported with some vedotin-containing drugs. The symptom list is therefore given according to the drug.

During follow-up, blood tests, imaging and symptom review are read together. The dose or date may be changed according to side effects and organ function. The list of medicines used at home is updated at every visit. Sudden fever, shortness of breath, uncontrolled diarrhoea or bleeding should be reported the same day.

Possible side effects

Fatigue, nausea, low blood cell counts, thinning of hair, changes in liver tests and infusion reactions may occur. The antibody part of the drug can carry effects related to its own target, and the payload part can carry effects similar to chemotherapy.

Shortness of breath, fever or severe diarrhoea should be reported without waiting. Dose reduction and postponement are used with these drugs as well.