What is Pembrolizumab (Keytruda) and How Does it Work to Fight Cancer?

Pembrolizumab (Keytruda) is a medication that can treat many types of cancer. It was initially approved in 2014 for melanoma, a type of skin cancer, but it’s since been approved for many other types of cancer.

Pembrolizumab works differently than chemotherapy — it’s a type of immunotherapy. Since its discovery, immunotherapy has become a game-changer in the treatment of cancer. It’s a newer approach to treating cancer, including advanced cancers and cancers that are historically hard to treat.

In this article, we’ll explore how pembrolizumab works and why it can be used in the treatment of so many types of cancer.

What is pembrolizumab (Keytruda)?

Pembrolizumab is an intravenous (IV) medication that’s injected into the bloodstream. At this time, it’s only available as a reference (“brand-name”) product. Specific doses vary by person, but it’s usually given once every 3 to 6 weeks. People may use it for up to 1 or 2 years. 

What is immunotherapy?

Immunotherapy is a type of cancer treatment that encourages the body’s immune system to find and attack cancer cells. This is different from traditional chemotherapy, which usually works by attacking cancer cells directly.

The immune system is the body’s natural defense against disease and infections. The immune system uses T cells — white blood cells that target substances they don’t recognize — to detect and kill other cells in the body, like cancer cells. Cancer cells and T cells can connect in the body through the PD-1/PD-L1 pathway. 

The PD-1/PD-L1 pathway helps balance the immune system’s response to cancer — it’s similar to having a gas and brake pedal on the immune system. However, cancer cells can take advantage of it and tell your immune system to always have its brakes on. Cancer cells then have the freedom to grow and spread.

More specifically, cancer cells hide from this pathway by having (or expressing) a protein called PD-L1 on their surfaces. This PD-L1 protein on cancer cells connects with a different protein, called PD-1, on T cells. When these two proteins bind together, the T cell isn’t able to destroy the cancer cell. This is like applying the brakes on the immune system. Immunotherapies like pembrolizumab aim to stop this connection and instead press the immune system’s gas pedal.

How does pembrolizumab (Keytruda) work?

Pembrolizumab is a monoclonal antibody medication, which is a lab-made protein that mimics human antibodies. It’s known as an immune checkpoint inhibitor, and it works by stopping PD-1. By stopping the connection between PD-1 and PD-L1, T cells can more easily find and destroy cancer cells.

Many different types of cancer can express PD-L1, which means that pembrolizumab can be effective for many cancers that use this method to escape the immune system. 

Depending on the stage and type of cancer, pembrolizumab may be given alone or in combination with a targeted therapy medication (drugs that work against specific cancer targets or mutations) or chemotherapy.

What are the FDA-approved uses of Keytruda?

Keytruda is approved to treat various types of cancer. As mentioned, it was initially approved to treat melanoma, but additional research has shown it can be effective for other types of cancer. This research has led the FDA to approve Keytruda for many types of cancer, including:

Skin cancers

• Melanoma: Melanoma is a rare type of skin cancer that forms in melanocytes — the cells that give the skin its color.

• Cutaneous squamous cell carcinoma: This is a more common type of skin cancer that forms in the outer layer of the skin.

• Merkel cell carcinoma: This is a rare type of skin cancer that occurs in Merkel cells found in the top layer of the skin.

Head and neck cancers

• Head and neck squamous cell cancer: This is a cancer that forms in places like the inside of the mouth, nose, and throat.

• Esophageal cancer: Esophageal cancer is a type of cancer that forms in the esophagus — the tube that connects the throat to the stomach.

Breast and lung cancers

• Non-small cell lung cancer: This is the most common type of lung cancer.

• Triple-negative breast cancer: This is a type of breast cancer that does not have any of the common receptors (chemical binding sites) found on breast cancer cells — the hormones estrogen and progesterone and a protein called HER2.

Gastrointestinal (GI) cancers

• Certain types of colorectal cancer: Colorectal cancer is a type of cancer that starts in the large intestine.

• Gastric cancer: This is a type of cancer that forms in the lining of the stomach.

Bladder and reproductive system cancers

• Renal cell carcinoma: This is a type of cancer that begins in the kidneys.

• Urothelial carcinoma: This is the most common type of cancer that starts in the bladder.

• Cervical cancer: This is a type of cancer that forms in the cervix, the lower part of the uterus.

• Endometrial carcinoma: This is a type of cancer that forms in the lining of the uterus called the endometrium.

Lymphoma

• Classical Hodgkin lymphoma: This is a cancer of the immune system that develops when lymphocytes — a type of white blood cell — start to grow out of control.

• Primary mediastinal large B-cell lymphoma: This is a rare type of non-Hodgkin lymphoma — a cancer of the immune system — that develops when the body makes abnormal B cells (a type of immune cell).

Other cancer types

• Tumor mutational burden-high (TMB-H) cancer: This is a type of cancer that has a high number of gene mutations, or changes, in the cancer cells. This is determined by a lab test.

• Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) cancer: This is a type of cancer that has a high amount of tumor instability. This happens when DNA repair genes stop working properly. This can be determined by a lab test.

Pembrolizumab is also being studied in clinical trials for the treatment of other types of cancer. It is likely that pembrolizumab will be approved for more uses in the future.

What is Keytruda’s success rate?

Pembrolizumab can treat a wide variety of cancers. It’s hard to narrow down one specific success rate. 

When it comes to melanoma, a 5-year follow up study found that pembrolizumab can help improve survival times compared to a similar medication (ipilimumab). The pair reported median survival times of close to 3 years and 1.5 years, respectively.

There are other Keytruda studies for different types of cancer, too. Pembrolizumab’s success rate slightly varies with each type of cancer. It can also change on a person-by-person basis. Based on your specific situation, your healthcare provider can help you estimate how effective the medication might be for you.

Is Keytruda better than chemotherapy?

It’s hard to say. It’s like comparing apples to oranges. Pembrolizumab and chemotherapy are frequently given in combination with each other, and they’re sometimes given at different points in your cancer journey. Still, some data is available to provide an idea of how they stack up.

A study of certain people with metastatic lung cancer showed that receiving pembrolizumab as a first-choice treatment nearly doubled 5-year survival rates — from about 16% to 32% — compared to people receiving chemotherapy. This means that more people were alive after 5 years when they received pembrolizumab instead of chemotherapy.

Another study of people with metastatic lung cancer showed that the combination of pembrolizumab and chemotherapy lowered the risk of death compared to people who only received standard chemotherapy.

How well pembrolizumab works depends on the type and stage of the cancer, as well as other factors, like the PD-L1 status of the tumor. You should discuss the best treatment option for you or a loved one with a cancer specialist.

How long does it take for immunotherapy using pembrolizumab to start working?

Chemotherapy can work quickly, and it’s possible to see tumors shrink shortly after starting treatment. By comparison, this isn’t usually the case for immunotherapy treatments like pembrolizumab. Since immunotherapy needs time to ramp up the immune system, it may take longer to see a response compared to chemotherapy. 

What side effects are associated with pembrolizumab (Keytruda)?

Like with all other medications, Keytruda has a number of potential risks and side effects. Some of the most common pembrolizumab side effects include: 

• Feeling tired

• Pain in muscles, bones, or joints 

• Itching

• Diarrhea or constipation

• Nausea

• Rash

• Fever

• Shortness of breath

Since immunotherapy helps the immune system attack cancer cells, it may also cause the immune system to attack normal cells in the body. These are called immune-mediated adverse events, which is like pressing the gas too much. While rare, pembrolizumab can cause these effects in different parts of the body, including: 

• Lungs: Inflammation of the lungs can lead to cough, shortness of breath, or chest pain.

• Intestines: Inflammation of the colon can lead to diarrhea, bloody stools, or severe stomach-area pain.

• Liver: Inflammation of the liver can lead to symptoms like yellowing of the skin or eyes (jaundice), severe nausea or vomiting, or pain on the right side of the stomach.

• Hormone glands: Pembrolizumab can affect different hormone glands in the body, like the thyroid gland. This may lead to symptoms like headaches that won’t go away, a rapid heartbeat, or extreme tiredness. These symptoms can mimic hypothyroidism or hyperthyroidism. 

• Kidneys: Inflammation of the kidneys can cause a lesser amount of urine, blood in the urine, or swelling of the ankles.

• Skin: Pembrolizumab can irritate the skin and cause symptoms like rash, itching, or skin blistering.

Since pembrolizumab is given as an infusion into a vein, it’s possible to have a reaction to the infusion. This can include shakiness, itching or rash, or flushing. Other symptoms may include shortness of breath, dizziness, or feeling like passing out. These reactions can happen during or after the infusion, and in some cases, may be severe or life-threatening.

People receiving pembrolizumab should be monitored closely for side effects. If side effects are severe or don’t go away, treatment may need to be stopped. 

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Written by:

Sonja Jacobsen, PharmD, BCPS, BCOP

Sonja Jacobsen, PharmD, BCPS, BCOP,  is a clinical oncology pharmacy specialist currently practicing in Seattle. She has been practicing as a pharmacist since 2015 and is licensed to practice in Washington state and North Carolina.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Emmeline C. Academia, PharmD, BCOP

Emmeline C. Academia, PharmD, BCOP, has been a practicing clinical pharmacist in adult oncology since 2020. She is a clinical pharmacy specialist in oncology at Beth Israel Deaconess Medical Center, in Boston.

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