Keytruda

Common Indications

Keytruda is used to treat many different types of cancer. It is often prescribed when cancer is advanced, has spread to other parts of the body (metastatic), or cannot be removed by surgery. In some cases, it is used as a preventive measure before or after surgery to reduce the risk of the cancer returning.

Types of Cancer

• Skin Cancers: This includes melanoma, Merkel cell carcinoma, and cutaneous squamous cell carcinoma.
• Lung Cancer: It is used for non-small cell lung cancer (NSCLC), sometimes as the first treatment or when other treatments have stopped working.
• Head and Neck Cancer: It is used for squamous cell carcinoma of the head and neck, including use before and after surgery for certain locally advanced cases.
• Breast Cancer: It is used for triple-negative breast cancer, typically in combination with chemotherapy.
• Gastrointestinal Cancers: This includes cancers of the esophagus, stomach (gastric cancer), and liver (hepatocellular carcinoma).
• Urinary and Kidney Cancers: It is used for urothelial carcinoma (bladder and urinary tract cancer) and renal cell carcinoma (kidney cancer).
• Gynecologic Cancers: It is used for cervical cancer, endometrial cancer, and certain types of ovarian, fallopian tube, or primary peritoneal cancers.
• Lymphoma: It is used for classical Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.

Genetic-Based Treatment

Keytruda is also used for tumors that have specific genetic markers, regardless of where the cancer originated in the body. These include:

• Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors.
• Tumor mutational burden-high (TMB-H) solid tumors.

These uses are generally reserved for patients whose cancer has progressed after previous treatments and who have no other satisfactory treatment options.

The Role of the Immune System

The immune system uses specialized cells called T-cells to find and destroy abnormal cells, including cancer. However, some cancer cells can produce proteins that trick the immune system into leaving them alone, allowing the cancer to grow and spread.

Blocking the PD-1 Pathway

Keytruda is a type of monoclonal antibody known as a PD-1 inhibitor. It targets a protein called programmed death receptor-1 (PD-1) located on the surface of T-cells. Many cancer cells use a related protein called PD-L1 to bind with PD-1, which sends a signal to the T-cell to stop its attack.

By blocking the PD-1 receptor, Keytruda prevents cancer cells from sending this signal. This action helps the immune system's T-cells stay active so they can better detect and destroy the cancer cells.

Immunotherapy vs. Chemotherapy

Unlike traditional chemotherapy, which works by directly killing fast-growing cells, Keytruda is an immunotherapy. This means it focuses on strengthening the body's natural defenses to fight the disease. It may be used as a primary treatment or alongside other therapies like surgery or chemotherapy.

Common Side Effects

The most frequently reported side effects for people taking Keytruda include:

• Fatigue and low energy
• Pain in the muscles, bones, or joints
• Nausea, diarrhea, or constipation
• Skin rash or itching
• Cough or shortness of breath
• Decreased appetite
• Fever

Serious Side Effects

Keytruda works by stimulating the immune system, which can sometimes cause it to attack healthy tissues and organs. These reactions can be severe or life-threatening and may occur during or after treatment. Seek medical attention immediately for symptoms involving the following:

• Lungs: New or worsening cough, shortness of breath, or chest pain.
• Digestive System: Severe stomach pain, diarrhea, or stools that are black, tarry, or contain blood or mucus.
• Liver: Yellowing of the skin or eyes, severe nausea, or dark urine.
• Hormone Glands: Persistent headaches, extreme tiredness, weight changes, increased thirst, or mood changes affecting the thyroid, pituitary, or adrenal glands.
• Kidneys: A change in the amount or color of urine.
• Skin: Severe rash, itching, skin blistering, or painful sores in the mouth, nose, or throat.

Infusion-related reactions may also occur during or shortly after the administration of the drug. Symptoms can include chills, shaking, dizziness, or feeling like you might pass out. Additionally, Keytruda may cause complications in people who have received an organ or bone marrow (stem cell) transplant.

Immune-Mediated Adverse Reactions

Keytruda works by helping the immune system fight cancer, but it can also cause the immune system to attack healthy tissues and organs. These reactions can occur at any time during treatment or even after treatment has stopped. Serious or life-threatening problems may affect the:

• Lungs: Inflammation (pneumonitis) that can cause shortness of breath or chest pain.
• Intestines: Inflammation (colitis) that can lead to diarrhea or severe stomach pain.
• Liver: Inflammation (hepatitis) that may cause yellowing of the skin or eyes (jaundice) and dark urine.
• Hormone Glands: Problems with the thyroid, pituitary, or adrenal glands, as well as the development of type 1 diabetes.
• Kidneys: Inflammation (nephritis) that can lead to kidney failure.
• Skin: Severe rashes, blistering, or peeling.

Infusion-Related Reactions

Some patients may experience reactions while receiving the medication or shortly after. Symptoms can include chills, shaking, itching, flushing, dizziness, or fever. Severe reactions require immediate medical attention and may require the treatment to be stopped.

Stem Cell Transplant Risks

There are increased risks of serious complications, including graft-versus-host disease (GVHD), in patients who receive an allogeneic hematopoietic stem cell transplant before or after treatment with Keytruda.

Pregnancy and Breastfeeding

Keytruda can cause harm to an unborn baby. Effective birth control is typically recommended during treatment and for at least four months after the final dose. Breastfeeding is generally not recommended during treatment and for four months after the last dose.

Monitoring

Healthcare providers perform regular blood tests to monitor liver function, kidney function, thyroid levels, and blood sugar levels to detect potential immune-mediated reactions early. Treatment may be delayed or permanently discontinued based on the severity of these reactions.

Pregnancy

Keytruda can cause harm to a developing fetus. Based on how the medication works, it may interfere with the immune system's ability to maintain a pregnancy, which could lead to pregnancy loss or fetal death. Healthcare providers typically advise against starting this medication during pregnancy unless the potential benefit outweighs the risks.

Individuals who can become pregnant should have a pregnancy test before starting treatment to ensure they are not pregnant. It is important to use effective contraception during treatment and for at least 4 months after the final dose of Keytruda. If a patient becomes pregnant while receiving this medication, they should notify their healthcare provider immediately.

Breastfeeding

It is currently unknown whether Keytruda passes into human breast milk. Because of the potential for serious adverse reactions in a nursing child, breastfeeding is not recommended during treatment and for at least 4 months following the last dose. Patients should discuss alternative feeding options with their healthcare team to ensure the safety of the infant.

Dosage Forms

Keytruda is supplied as a solution for injection. It is available in the following formats:

• Intravenous Infusion: This form is a clear to slightly opalescent, colorless to pale yellow solution supplied in a single-dose vial. A healthcare professional dilutes this solution before administering it through an intravenous (IV) line.
• Subcutaneous Injection: A formulation containing pembrolizumab and berahyaluronidase alfa-pmph is available for injection under the skin (subcutaneously).

FDA Approval Status

Keytruda is approved by the U.S. Food and Drug Administration (FDA) for the treatment of numerous types of advanced or metastatic cancers. It belongs to a class of drugs known as PD-1 inhibitors, which help the immune system detect and attack cancer cells. The medication is approved for use in both adult and pediatric patients for specific indications, often depending on whether the cancer expresses certain biomarkers or has progressed after other treatments.

Recent Regulatory Actions

• Head and Neck Cancer: The FDA recently approved pembrolizumab for use before surgery (neoadjuvant) in combination with chemotherapy, and then continued as a single agent after surgery (adjuvant), for resectable locally advanced head and neck squamous cell carcinoma (HNSCC).
• Ovarian Cancer: Approval was granted for use in combination with paclitaxel for patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.
• Subcutaneous Administration: In addition to the standard intravenous (IV) formulation, the FDA approved a subcutaneous injection version (pembrolizumab and hyaluronidase-alfa-pmph) for several indications previously approved for the IV version.

Safety Monitoring

Keytruda is a prescription-only medication. While it does not currently have a boxed warning, it is subject to ongoing monitoring for immune-related adverse reactions, which are a known risk of this class of immunotherapy. There are no specific Risk Evaluation and Mitigation Strategy (REMS) programs currently required for its use beyond standard clinical monitoring and patient medication guides.

Keytruda is a prescription medication that must be administered by a healthcare professional in a medical setting. Because it is not a drug patients can purchase and administer themselves, the total cost is often tied to the professional services and the facility where treatment occurs.

Factors Influencing Cost

• Administration Method: Keytruda is typically delivered as an intravenous (IV) infusion. However, some versions are approved for administration as a subcutaneous injection. The method used may affect the overall cost of the procedure.
• Treatment Schedule: The frequency of doses and the total duration of therapy are determined by the healthcare provider based on the specific condition being treated and how the patient responds to the medication.
• Clinical Setting: The medication is given in hospitals, clinics, or infusion centers. Costs can vary based on the specific facility and the professional monitoring required during administration.

Patients should consult with their healthcare provider or insurance carrier to obtain specific pricing information and to understand their coverage options for this treatment.