Pembrolizumab

Approved Indications

Pembrolizumab is a prescription immunotherapy used to treat a wide variety of cancers. It is often prescribed for cancers that have spread to other parts of the body (metastatic), cannot be surgically removed, or have returned after previous treatments. It may be used alone or in combination with chemotherapy or other targeted drugs.

Commonly Treated Cancers

• Skin Cancers: Advanced melanoma, Merkel cell carcinoma, and cutaneous squamous cell carcinoma.
• Lung Cancers: Non-small cell lung cancer (NSCLC).
• Head and Neck Cancers: Squamous cell carcinoma of the head and neck.
• Blood Cancers: Classical Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.
• Genitourinary Cancers: Bladder (urothelial) cancer and kidney (renal cell) cancer.
• Gastrointestinal Cancers: Esophageal cancer, gastric (stomach) cancer (including HER2-positive cases), and liver cancer (hepatocellular carcinoma).
• Gynecologic Cancers: Cervical cancer, endometrial cancer, and platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.
• Breast Cancer: Triple-negative breast cancer.

Biomarker-Specific Use

Pembrolizumab is used for solid tumors that are identified by specific laboratory tests as being microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This applies when the cancer has progressed following other treatments and there are no satisfactory alternative options.

Adjuvant Therapy

This medication is also used as an adjuvant treatment, meaning it is given after surgery to help reduce the risk of certain cancers, such as melanoma or lung cancer, from coming back.

The Immune System and Cancer

The immune system uses specialized white blood cells called T cells to find and destroy threats, such as infections or abnormal cells. However, cancer cells can sometimes develop ways to "hide" from these T cells, allowing the cancer to grow and spread without being attacked.

Blocking the PD-1 Pathway

Pembrolizumab is a monoclonal antibody that belongs to a class of drugs known as PD-1 inhibitors. PD-1 is a protein found on the surface of T cells that acts as a "checkpoint" or a brake. When PD-1 attaches to other proteins (called PD-L1 or PD-L2) found on some normal cells and cancer cells, it sends a signal to the T cell to stop attacking.

Many types of cancer cells produce these proteins to trick the immune system into leaving them alone. By binding to the PD-1 protein, pembrolizumab prevents it from connecting with the cancer cells' proteins. This action effectively "releases the brakes" on the immune system.

Reactivating T Cells

When the PD-1 pathway is blocked, T cells are better able to:

• Recognize cancer cells as a threat.
• Increase their activity and multiply.
• Target and attack the tumor cells throughout the body.

Because this treatment works by enhancing the body's natural defenses rather than attacking cells directly like traditional chemotherapy, it is classified as an immunotherapy.

Common Side Effects

Many people experience side effects while receiving pembrolizumab. Common symptoms may include:

• Fatigue or weakness
• Nausea, diarrhea, or constipation
• Decreased appetite
• Itching or skin rash
• Cough or shortness of breath
• Muscle, bone, or joint pain
• Fever
• Stomach pain

Serious Side Effects

Pembrolizumab can cause the immune system to attack healthy organs. These reactions can be severe or life-threatening and may occur during or after treatment. Seek medical help immediately for:

• Lung problems: New or worsening cough, shortness of breath, or chest pain.
• Intestinal problems: Severe diarrhea, stomach pain, or stools that are bloody or tarry.
• Liver problems: Yellowing of the skin or eyes, dark urine, or severe nausea.
• Hormone problems: Rapid heartbeat, extreme tiredness, weight changes, or mood changes.
• Kidney problems: Changes in urine color or amount, or swelling in the ankles.
• Skin reactions: Severe rash, blistering, or peeling skin.
• Infusion reactions: Dizziness, chills, or flushing during the injection.

Other serious complications can include organ transplant rejection or graft-versus-host disease in patients who have received a stem cell transplant.

Immune-Mediated Adverse Reactions

Pembrolizumab works by stimulating the immune system to attack cancer cells. However, it can also cause the immune system to attack normal organs and tissues in any part of the body. These reactions can be severe or fatal and may occur during treatment or months after the final dose.

• Lung Problems: Inflammation of the lungs (pneumonitis) can occur. Symptoms may include a new or worsening cough, chest pain, or shortness of breath.
• Intestinal Problems: Inflammation of the colon (colitis) can lead to diarrhea, severe stomach pain, or blood in the stool.
• Liver Problems: Hepatitis or liver inflammation may cause yellowing of the skin or eyes (jaundice), dark urine, or severe nausea and vomiting.
• Hormone Gland Problems: The drug can affect the thyroid, pituitary, and adrenal glands, as well as the pancreas. This may lead to conditions such as type 1 diabetes or thyroid disorders.
• Kidney Problems: Inflammation of the kidneys (nephritis) can cause changes in the amount or color of urine.
• Skin Problems: Severe rashes, itching, blistering, or peeling can occur.

Infusion-Related Reactions

Severe or life-threatening reactions can occur during or shortly after the administration of the medication. Symptoms may include chills, shaking, itching, flushing, dizziness, fever, or difficulty breathing.

Stem Cell Transplant Risks

Serious and potentially fatal complications can occur in patients who receive an allogeneic hematopoietic stem cell transplant (using donor cells) before or after treatment with pembrolizumab. These complications include graft-versus-host disease and other immune-related issues.

Pregnancy and Breastfeeding

Pembrolizumab 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 advised during treatment and for four months following the last dose due to the risk of serious side effects in the infant.

Monitoring

Regular blood tests are necessary to monitor liver function, kidney function, and hormone levels. Healthcare providers use these tests to detect immune-mediated reactions early, even if symptoms are not yet present.

Pregnancy

Pembrolizumab can cause harm to a fetus when administered to a pregnant person. Before starting treatment, healthcare providers typically perform a pregnancy test to confirm that a patient is not pregnant. It is important to use effective birth control (contraception) during treatment and for at least 4 months after the final dose of the medication.

If you become pregnant or think you might be pregnant while receiving this medication, notify your healthcare provider immediately to discuss the potential risks to the fetus.

Breastfeeding

It is not known if pembrolizumab passes into human breast milk. Because of the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended during treatment and for at least 4 months after the last dose. Patients should discuss the best way to feed their baby with their healthcare team during this time.

Available Forms

Pembrolizumab is provided in the following dosage forms:

• Intravenous Solution: A liquid solution supplied in single-dose vials for infusion into a vein.
• Subcutaneous Injection: A formulation combined with berahyaluronidase-alfa-pmph for injection under the skin.

Administration

This medication is administered by a doctor or nurse in a hospital or clinical facility. The intravenous infusion typically takes about 30 minutes. The specific dose and schedule are determined by a healthcare provider based on the patient's weight, the condition being treated, and how well the body responds to the medication.

FDA Approval Status

Pembrolizumab was first approved by the U.S. Food and Drug Administration (FDA) in 2014. It is classified as a programmed death receptor-1 (PD-1) blocking antibody. While originally approved as an intravenous (IV) medication, the FDA approved a subcutaneous version (pembrolizumab and hyaluronidase-alfa-pmph) in June 2024 for several adult indications.

Approved Indications

The FDA has approved pembrolizumab for numerous types of cancer, often based on specific genetic markers or previous treatment history. Key indications include:

• Melanoma
• Non-small cell lung cancer (NSCLC)
• Head and neck squamous cell carcinoma
• Classical Hodgkin lymphoma
• Urothelial carcinoma
• Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) cancers
• Gastric or gastroesophageal junction adenocarcinoma
• Cervical cancer
• Triple-negative breast cancer

Recent regulatory actions include the June 2024 approval for use in combination with paclitaxel for patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. It is also approved for use with trastuzumab and chemotherapy for certain HER2-positive gastric cancers.

Safety and Monitoring

There are currently no FDA Boxed Warnings for pembrolizumab. However, the FDA monitors the drug for immune-related adverse reactions, which can affect various organs including the lungs, colon, liver, endocrine glands, and kidneys. Regulatory approval for certain uses may require specific diagnostic testing, such as PD-L1 expression levels or MSI-H/dMMR status, to determine if a patient is a candidate for treatment.

Factors Affecting Cost

The total price of pembrolizumab treatment is influenced by several variables:

• Dosage and Schedule: The specific dose and the frequency of administration (such as every three or six weeks) impact the overall cost.
• Administration Method: Costs may vary between intravenous infusion and subcutaneous injection, as well as the fees associated with the healthcare facility providing the service.
• Insurance Coverage: Most insurance providers, including Medicare and Medicaid, cover pembrolizumab for FDA-approved uses. However, out-of-pocket expenses like copays and deductibles can vary widely between plans.

Financial Assistance Programs

Because immunotherapy can be expensive, financial support options may be available to help patients manage costs:

• Manufacturer Assistance: The drug manufacturer may offer patient assistance programs or co-pay coupons for those who meet specific eligibility criteria.
• Charitable Foundations: Independent organizations sometimes provide grants to help cover the costs of cancer treatments for patients with financial need.

Patients should consult with their oncology team or hospital billing department to get an accurate estimate of costs and to explore available financial resources.