Antibody-drug conjugates (ADCs) are transforming oncology treatment for breast cancer patients (and other patients, too! They can be used in different cancer treatment regimens.) ADCs are founded in the concept of a “magic bullet,” which was developed by Paul Ehrlich, the founder of chemotherapy treatment. Paul Ehrlich’s work was done over 100 years ago- he won the Nobel Prize for Physiology or Medicine in 1908- but it formed the basis for treatment options that we are seeing today.

The magic bullet theory is one he developed after years of working with dyes and their affinities for certain parts of cells, and then working in immunology. His theory introduced the idea of drugs that would go directly to their intended structural target-the very heart of targeted treatments. Targeted treatment, by definition, goes to the cells that it needs to, thereby leaving the healthy cells intact. It’s the sniper of the anti-neoplastic world (fyi: anti-neoplastics are any medications used against malignant tumors). This is important because one of the biggest concerns for cancer patients is the balancing act of administering treatments while minimizing side effects or making the treatment tolerable. Targeted therapies typically have a greater tolerability than their chemo counterparts.

Here’s a little visual:

Targeted therapy:

Regular ole chemotherapy:

ADCs combine the precision of the monoclonal antibodies with the power of chemotherapy. This means that the drug targets cancer cells, delivering the toxic drugs (or “payload”) right into them. ADCs consist of the monoclonal antibody, the payload, and a linker- the way that the antibody is able to deliver the payload to the cancer.

Think of the chopper as the monoclonal antibody, and that little package hanging off the end is the chemo:

Some of these drugs even have what is called the “bystander effect.” The payload portion of the conjugate is membrane permeable, and can migrate out of the cancer cell where it was delivered, potentially affecting nearby cancer cells that have a high target expression. The payload portion of ADCs can be even more potent than what is given with traditional chemo. This is because the drug is going right to the place where it’s needed, and not the healthy tissue around it.

Something that I think is really cool is that ADCs are showing a clinically noticeable response even in tumors that don’t have a really high target expression, meaning they have a low number of target antigens on the outside of the cells that the targeted component of the ADC is looking for. This is good news!

There are four ADCs used in the treatment of breast cancer:

TDM-1 (trastuzumab emtansine or Kadcyla)- used in HER2-positive breast cancer, both early and metastatic.

T-DXd (trastuzumab deruxtecan or Enhertu)- used in metastatic HER2-positive and HER2-low breast cancer and now, more recently, has FDA approval for HER2-positive, early stage breast cancer.

SG (sacituzumab govitecan or Trodelvy)- for triple-negative breast cancer, and certain metastatic cases of HR-positive, HER2-negative breast cancer

Dato-DXd (datopotamab deruxtecan or Datroway)- for certain triple-negative breast cancer patients, and certain HR-positive, HER2-negative breast cancer patients.

Phew. It’s a lot. If you or someone you know is experiencing breast cancer, they may have been offered one of these medications as an option. They all have their own safety and side-effect profiles and let’s just say- little quirks.

Kadcyla- common side effects include headache and fatigue, nausea and constipation, musculoskeletal pain, thrombocytopenia (low platelets), and peripheral neuropathy.

Enhertu- common side effects include nausea, low white blood cells, low red blood cells, fatigue, low platelets, vomiting, increased liver function tests.

Trodelvy- common side effects include fatigue, nausea, and hair loss. It also has a box warning for neutropenia and diarrhea, so this one may require a white blood cells booster shot afterwards (growth factors or GCSFs). Your doctor may want you to take anti-diarrheals as well.

Datroway- can cause mouth sores, nausea, and hair loss. It can be constipating and cause fatigue. This one requires the use of a steroid mouth wash and also eye drops to prevent eye problems. It is harmful to unborn babies, so it can’t be used during pregnancy. Your nurse will give you ice to eat while you are getting your infusion, to help reduce the mouth sores which can be serious. The ice constricts blood vessels in the mouth and throat which means that less of the infusion medication is able to reach those spots.

All things considered, these medications are providing options and a literal lifeline to patients in the oncology world.

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