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. The approval for pembrolizumab is the first time the FDA has approved a medicine 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 cancers that have a solid tumor 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)
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.
Right now, the only people approved to get pembrolizumab outside of a clinical trial have cancer that
- can’t be removed surgically, and
- is found to be microsatellite instability-high or mismatch repair deficient and
- has grown after treatment with other medicines
But recent and ongoing trials may mean more people become eligible in the future.
Results from the I-SPY 2 trial were presented at the American Society of Clinical Oncology Annual Meeting in June 2017. This trial showed that people with HER2-negative breast cancers did better when given pembrolizumab alongside chemotherapy before surgery compared to chemotherapy alone. The biggest response to pembrolizumab was seen in people who had triple-negative breast cancer, with 60 percent having a pathological complete response on pembrolizumab compared to 20 percent of those who were given just chemotherapy.
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 show in effects such as inflammation of endocrine glands, of the colon, of the lungs, or in immune cells causing damage to the liver.