Pembrolizumab (Keytruda) is an anti-PD-1 immunotherapyinfo-icon medicineinfo-icon that uses the body’s immune systeminfo-icon to attack cancer cells.

Usually, the FDAinfo-icon 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 tumorinfo-icon that cannot be removed with surgeryinfo-icon or has traveled away from the original site (become metastaticinfo-icon), 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.

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

Right now, the only people approved to get pembrolizumab outside of a clinical trialinfo-icon 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 Clinicalinfo-icon Oncologyinfo-icon Annual Meeting in June 2017. This trial showed that people with HER2-negative breast cancers did better when given pembrolizumab alongside chemotherapyinfo-icon before surgeryinfo-icon compared to chemotherapy alone. The biggest response to pembrolizumab was seen in people who had triple-negative breast cancerinfo-icon, with 60 percent having a pathological complete responseinfo-icon on pembrolizumab compared to 20 percent of those who were given just chemotherapy. 

How Do I Know if the Cancer is Microsatellite Instability-High or Mismatch Repair Deficient?

Microsatellite Instability-high and mismatch pair deficient tumors can be identified with common lab tests performed on tumorinfo-icon samples from your biopsyinfo-icon, such as an immunohistochemistryinfo-icon test or a genomic test

How Pembrolizumab is Given

Pembrolizumab is given by veininfo-icon. Currently it is given in 30 minute infusioninfo-icon sessions once every 3 weeks. 

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 show in effects such as inflammationinfo-icon of endocrineinfo-icon glands, of the colon, of the lungs, or in immune cells causing damage to the liver. 

December 12, 2017