Adjuvant Pembrolizumab in Renal Cell Carcinoma - An Overview

Introduction:

Pembrolizumab is a drug that is used to treat many types of cancer. It is used to treat intermediate to high-risk cancers in nature. Numerous trials were conducted in humans that proved the use of Pembrolizumab along with other cancer drugs to be useful. The United States Food and Drug Administration (FDA) has approved the use of this drug along with other medicines in the year 2021. The type of therapy that this drug provides is called immunotherapy. FDA collaborated with other regulatory authorities of countries like Australia, Canada, and Sweden to provide a review on these recently conducted trials and other cancer drugs as well.

What Is Immunotherapy?

• Immunotherapy is a treatment that facilitates the killing of cancer cells by the body’s immune system.

• Immunotherapy is also called biological therapy since it uses biological substances that are made or derived from living organisms.

• The immune system, as we all know, helps the body to fight against various infections and protects us from serious diseases. It also detects and kills abnormal cells in the body, which might develop into cancer.

• The mere presence of immunity in the body cannot prevent the body from forming cancer cells.

• Sometimes, the cancer cells develop and form cancer despite a good immune system. These instances are, for example, genetic mutations and hereditary genetic syndromes.

• Immunotherapy helps the body’s defense system in detecting and killing cancer cells in a better way.

What Are the Types of Immunotherapy?

1. Immune Checkpoint Inhibitors: This type of therapy uses drugs that block the checkpoints of immune cells, thereby increasing the immune response of immune cells.

2. T-Cell Transfer Therapy: T-cells are one of the types of lymphocytes that help in protecting the body against infections and cancer as well. This therapy uses drugs that enhance the existing natural ability of the T-cells to fight against cancer. T-cell transfer therapy is also called adoptive cell therapy and adoptive immunotherapy.

3. Monoclonal Antibodies: They are the proteins that bind to specific targets on immune cells, thereby highlighting them and being better detected by the immune system. These are made in laboratories and act as the body’s antibodies.

4. Treatment Vaccines: Few vaccines are capable of protecting and fighting against cancer. Such vaccines are called treatment vaccines. A few examples are the human papillomavirus vaccine (HPV) and the hepatitis B vaccine.

5. Immune System Modulators: A substance that modifies the response of the immune system to fight against various infections, diseases, and cancer is called an immune system modulator. A few examples are cytokines and monoclonal antibodies. A few examples of natural immune system modulators are curcumin and genistein.

What Is Pembrolizumab?

• Pembrolizumab is an anticancer drug that is used to treat several cancers of the body. It is a monoclonal antibody that is directed against a specific human cell receptor that regulates cell death.

• Pembrolizumab has antineoplastic ability and also inhibits the immune checkpoint response, thereby enhancing the body’s immune response against cancer cells.

• Pembrolizumab is a type of immunotherapy that helps the body's immune system to fight against cancer.

• It was approved for medical use in the United States in the year 2014.

• In 2017 it received approval by the United States Food and Drug Administration for use in tumors that cannot be removed through surgery and in solid metastatic tumors with genetic abnormalities.

• The drug is marketed under the brand name Keytruda.

• In 2021, Food and Drug Administration approved its use as adjuvant therapy in renal cell carcinoma.

How Does Pembrolizumab Treat Cancer?

Since we already learned that Pembrolizumab is a drug that is used as immunotherapy in cancer, we shall know how it helps in treating cancer:

• It is a monoclonal antibody that is prepared in the laboratory to restore, enhance, modify and mimic immune cells.

• It is an immunoglobulin G4 isotype antibody that blocks the protective system of cancer cells, thereby allowing the body’s natural immune system to respond to cancer.

• It binds to a specific cell receptor (PD1- programmed cell death 1) that regulates cell death.

• This receptor is called an immune checkpoint.

• Pembrolizumab binds to this PD1 receptor, thereby blocking and deactivating its cell-mediated immune response.

• This blockade is the key aspect of the way of targeting and killing cancer cells.

• Genetic mutations cause an immune response to the numerous proteins that further serve as tumor antigens. These antigens can be destroyed by Pembrolizumab by preventing the checkpoint immune response and by blocking T-cells (lymphocytes or white blood cells).

How Is Pembrolizumab Used?

It is injected into the body through veins, intravenous route (IV) for treatment of cancer. It can be injected into the body in the following methods:

1. Central Line: The central line or central venous line is used by placing a large catheter either in the neck or upper neck. This method can be used for a longer duration. It is easier and causes less discomfort.

2. PICC: Peripherally inserted central catheter (PICC) is also a type of central line that uses a long flexible catheter inserted into the upper arm. This line gives the doctor access to the large central veins near the heart. This line is used to deliver chemotherapy, nutrition, and fluids into the body.

3. Portacath: This is a small device that is used to draw blood, deliver treatments, and for blood transfusion purposes. This device is attached to a thin, flexible catheter that is inserted into a large vein just above the right side of the heart.

How Often Can Pembrolizumab Be Used?

The duration and intensity of the treatment often depend upon the stage of cancer. Every patient will have a customized treatment plan prepared by the doctor that is best for the individual. However, a generalized dosage regimen would be:

• The frequency would be every three to six weeks.

• The treatment continues for up to two years for most renal cell carcinomas.

• It is available in the dosage form of 100 mg/ml solution in a single vial.

This dosage form is available in the market as approved by the Food and Drug Administration. However, the intensity and frequency of using the Pembrolizumab must be decided by the doctor for the benefit of the patient.

What Are the Side Effects of Pembrolizumab?

• Reduced red blood cell count (RBC) or anemia.

• Tiredness or lack of energy (fatigue).

• Increased glucose levels (hyperglycemia).

• Reduced potassium levels (Hyponatremia).

• Itching.

• Cough.

• Vomiting sensation (nausea).

• Reduced hunger (appetite loss).

• Reduced calcium (hypocalcemia).

• Constipation.

• Headache.

• Chills (shivering).

• Joint pain (arthralgia).

• Muscle pain (myalgia).

• Back pain.

• Abdominal pain.

• Diarrhea.

• Sleeplessness (insomnia).

• Swelling.

• Shortness of breath (difficulty breathing).

Is Pembrolizumab Approved in India to Use It as an Adjuvant in Cancer Therapy?

• It was approved by the Drug Controller General Of India (DCGI) for its use as an adjuvant in cancer treatment in the year 2021. After the FDA had approved its use in the United States, DCGI also approved its use in India.

Conclusion:

The use of Pembrolizumab, along with other chemotherapy and surgical procedures in patients with kidney cancer, has shown a significant increase in disease-free survival. The major and favorable outcomes of the use of Pembrolizumab were two, of which one is disease-free survival and the second one is overall survival.