Pembrolizumab (Keytruda) is an anti-PD-1 immunotherapy medicine that uses the body’s immune systeminfo-icon to attack cancer cells. It is approved by the Food and Drug Administrationinfo-icon to be given with chemotherapyinfo-icon to treat people with metastaticinfo-icon, triple-negative breast cancerinfo-icon that expresses the PD-L1 proteininfo-icon. It is also approved to treat cancers — including breast cancer and several other types — that have certain characteristics.

Studies are ongoing to find out if there are other features that show a cancer may respond to pembrolizumab.

How pembrolizumab works

Pembrolizumab is a humanized monoclonal immunoglobulin antibody that targets a proteininfo-icon present on the surface of certain white blood cells, including cells called T lymphocytes or “T cells.” This protein, called PD-1, has an important role in regulating the immune systeminfo-icon. Your cells bind to PD-1 on the T cells as a way of telling your immune system that they are part of your body and should not be attacked.

Most diseases come from outside your body and don’t have the protein to bind with the PD-1 receptorinfo-icon. When a T cellinfo-icon comes across a cell that cannot bind because it doesn’t have the protein, the T cell destroys the unrecognized cell. Cancer cells are mutated versions of your own healthy cells, which means they have the same proteins that bind to PD-1 receptors. When a T cell encounters a cancer cell, the protein tells the T cell that the cancer cell is part of the body and it should not attack.

Pembrolizumab works on the T cells by blocking the work of the PD-1 receptors, releasing the brakes from the immune system to kill cancer. The cancer cells, unable to bind to the T cells, are destroyed. In that way pembrolizumab is an immunotherapyinfo-icon, meaning it uses your immune system to treat the cancer.

Who gets pembrolizumab

Pembrolizumab for breast cancer

Pembrolizumab is approved to be given with chemotherapyinfo-icon to treat metastaticinfo-icon, triple-negative breast cancerinfo-icon that expresses the PD-L1 proteininfo-icon. If your medical team thinks you may benefit from pembrolizumab, they will use an FDAinfo-icon-approved test on a sample of cancer tissueinfo-icon that was taken during surgeryinfo-icon or a biopsyinfo-icon for the level of PD-L1 expression.

Pembrolizumab for solid tumors

Usually, the FDA approves medicines to treat certain kinds of cancer, identified by their location in the body. A medicineinfo-icon might be approved for breast cancer or for lung cancer. Some medicines have been approved for multiple types of cancer, but have been approved for each separately. Pembrolizumab is the first medicine approved to treat any cancer that has certain characteristics, regardless of where in the body it started.

This approval means pembrolizumab can be used in breast cancer, and also lung cancer, colon cancer and cancers of other parts of the body. The FDA approved it to treat solid tumors that cannot be removed with surgery or has traveled away from the original site (become metastatic), and tests positive as either

  • microsatellite instability-high (MSI-H)
  • mismatch repair deficient (dMMR)
  • high tumorinfo-icon mutational burden (TMB)

Microsatellite instability-high and mismatch pair deficient tumors can be identified with common lab tests performed on tumor samples from your biopsy, such as an immunohistochemistryinfo-icon test or a genomic testinfo-icon. Tumor mutational burden (TMB) can be identified with genomic tests.

How pembrolizumab is given

Pembrolizumab is given through a port or a line placed with a needle to drip medicineinfo-icon directly into a veininfo-icon, a process called infusioninfo-icon. It may be given in a 200 milligram doseinfo-icon once every 3 weeks, or a 400 milligram dose once every 6 weeks.

For triple-negative breast cancerinfo-icon that is PD-L1 positive, pembrolizumab is given with chemotherapyinfo-icon that will also be given by infusion. For cancers that are microsatellite instability-high or mismatch pair deficient, or have high TMB, pembrolizumab can be given on its own. 

Side effects and things to remember

According to its FDAinfo-icon approval, the most common side effects of pembrolizumab are

Because pembrolizumab affects the way your immune systeminfo-icon recognizes your cells, it also may cause your immune system to target healthy cells in your body. Like the cancer cells, your healthy cells may not be able to bind to T cells, causing the T cells to attack. This could result in side effects such as inflammationinfo-icon of endocrineinfo-icon glands, the colon, or the lungs, or in immune cells causing damage to the liver. 

February 12, 2021