Pembrolizumab (Keytruda) is an anti-PD-1 immunotherapy medicine that uses the body’s immune system to attack cancer cells. It is approved by the Food and Drug Administration to be given with chemotherapy to treat people with metastatic, triple-negative breast cancer that expresses the PD-L1 protein. 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.
Pembrolizumab is a humanized monoclonal immunoglobulin antibody that targets a protein 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 system. 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 receptor. When a T cell 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 immunotherapy, meaning it uses your immune system to treat the cancer.
Pembrolizumab for breast cancer
Pembrolizumab is approved to be given with chemotherapy to treat metastatic, triple-negative breast cancer that expresses the PD-L1 protein. If your medical team thinks you may benefit from pembrolizumab, they will use an FDA-approved test on a sample of cancer tissue that was taken during surgery or a biopsy 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 medicine 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 tumor 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 immunohistochemistry test or a genomic test. Tumor mutational burden (TMB) can be identified with genomic tests.
Pembrolizumab is given through a port or a line placed with a needle to drip medicine directly into a vein, a process called infusion. It may be given in a 200 milligram dose once every 3 weeks, or a 400 milligram dose once every 6 weeks.
For triple-negative breast cancer that is PD-L1 positive, pembrolizumab is given with chemotherapy 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.
According to its FDA approval, the most common side effects of pembrolizumab are
- Severe itching
- Loss of appetite
- Difficulty breathing
Because pembrolizumab affects the way your immune system 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 inflammation of endocrine glands, the colon, or the lungs, or in immune cells causing damage to the liver.