Durvalumab

Lung Cancer

Durvalumab is used to treat specific types of lung cancer based on the stage of the disease and previous treatments:

• Non-small cell lung cancer: It is used for cancer that has not spread to other parts of the body but cannot be removed by surgery. It is typically given after the patient has already received chemotherapy and radiation.
• Small cell lung cancer: It is used for extensive-stage cancer in combination with chemotherapy. It is also used for limited-stage cancer that has not worsened after receiving chemotherapy and radiation at the same time.

Biliary Tract and Liver Cancers

This medication is used for cancers affecting the digestive system:

• Biliary tract cancer: It is used with chemotherapy for adults with cancer of the bile ducts or gallbladder that has spread or cannot be removed by surgery.
• Liver cancer: It is used in combination with another medication for adults with a type of primary liver cancer (hepatocellular carcinoma) that cannot be removed by surgery.

Bladder and Stomach Cancers

Durvalumab is also approved for the following conditions:

• Bladder cancer: It is used with chemotherapy for adults with muscle-invasive bladder cancer before surgery, and then continued alone after surgery.
• Stomach and esophageal cancer: It is used with chemotherapy for adults with certain types of stomach cancer or cancer of the area where the esophagus meets the stomach (gastroesophageal junction) before surgery, and then continued alone after surgery.

Mechanism of Action

Durvalumab belongs to a class of drugs known as PD-L1 inhibitors. It is a monoclonal antibody designed to target specific proteins that cancer cells use to hide from the immune system.

The immune system uses checkpoints to prevent it from attacking healthy cells. Some cancer cells exploit these checkpoints by producing a protein called programmed death-ligand 1 (PD-L1). When PD-L1 binds to certain receptors on T-cells, which are the immune system's primary defense cells, it sends a signal that tells the T-cells not to attack.

Durvalumab works by:

• Binding directly to the PD-L1 protein on the surface of cancer cells or other cells within the tumor.
• Blocking PD-L1 from interacting with the PD-1 and CD80 receptors on T-cells.
• Removing the signal that prevents the immune system from attacking, which allows T-cells to identify and destroy the cancer cells more effectively.

Common Side Effects

The most frequently reported side effects of durvalumab include:

• Fatigue and weakness
• Muscle, joint, or bone pain
• Nausea and vomiting
• Constipation or diarrhea
• Decreased appetite
• Cough or shortness of breath
• Rash or itchy skin
• Hair loss
• Swelling in the hands, feet, or ankles
• Upper respiratory tract infections

Serious Side Effects

Durvalumab can cause the immune system to attack healthy parts of the body, leading to serious or life-threatening conditions. Seek medical attention immediately for symptoms of:

• Lung problems: New or worsening cough, shortness of breath, or chest pain.
• Intestinal problems: Severe stomach pain, diarrhea, or stools that are black, tarry, or contain blood.
• Liver problems: Yellowing of the skin or eyes (jaundice), dark urine, or severe nausea and vomiting.
• Hormone gland issues: Persistent headaches, extreme tiredness, weight changes, dizziness, or changes in mood. This may involve the thyroid, adrenal, or pituitary glands.
• Kidney problems: Decrease in urine output or blood in the urine.
• Severe skin reactions: Rash with blisters, peeling, or sores in the mouth or nose.
• Infusion-related reactions: Fever, chills, flushing, or wheezing during the injection.

Immune-Mediated Adverse Reactions

Durvalumab works by helping the immune system attack cancer cells. However, it can also cause the immune system to attack normal parts of the body. These reactions can happen in any organ or tissue and may occur during treatment or after treatment has stopped. Serious or fatal reactions have been reported.

Organ Inflammation

• Lungs: Inflammation of the lungs (pneumonitis) can cause new or worsening cough, chest pain, or shortness of breath.
• Liver: Hepatitis can lead to yellowing of the skin or eyes (jaundice), severe nausea, dark urine, or pain on the right side of the stomach area.
• Intestines: Colitis can cause diarrhea, more frequent bowel movements than usual, or stools that are black, tarry, or contain blood or mucus.
• Hormone Glands: Problems with the thyroid, pituitary, or adrenal glands can cause extreme tiredness, weight changes, mood changes, or dizziness.
• Kidneys: Nephritis can result in changes in the amount or color of urine, or swelling in the ankles.
• Skin: Severe rashes, itching, or blistering may occur.

Infusion-Related Reactions

Some people may experience a reaction while receiving the medication through an intravenous (IV) infusion. Symptoms may include chills, shaking, itching, flushing, wheezing, or fever.

Pregnancy and Breastfeeding

Durvalumab can cause harm to an unborn baby. It is generally recommended that individuals who can become pregnant use effective birth control during treatment and for several months after the final dose. Breastfeeding is typically not recommended during treatment and for a period following the last dose.

Monitoring

Healthcare providers typically monitor patients closely through physical exams and blood tests to check liver, kidney, and thyroid function. Early detection of immune-mediated reactions is critical for managing these side effects, which may require stopping treatment or starting corticosteroid medications.

Pregnancy

Durvalumab can cause harm to a developing fetus. It is important to discuss the risks and benefits with a healthcare provider if you are pregnant or planning to become pregnant. Individuals who can become pregnant should use effective birth control during treatment and for at least 3 months after the last dose of the medication.

Breastfeeding

It is not known whether durvalumab passes into human breast milk. Due to the risk of serious side effects in a nursing child, breastfeeding is not recommended during treatment. Patients are typically advised to wait at least 3 months after their final dose before breastfeeding.

Available Forms

Durvalumab is supplied as a sterile, preservative-free solution. It is provided in single-dose vials for administration as an intravenous infusion.

• Injection: A liquid solution intended for dilution and infusion into a vein.

FDA Approval Status

Durvalumab is approved by the U.S. Food and Drug Administration (FDA) for the treatment of various malignancies. It is often used as a first-line treatment or after other therapies, such as chemotherapy and radiation, have been completed.

Approved Indications

The FDA has approved durvalumab for the following uses:

• Lung Cancer: It is used for adults with Stage III non-small cell lung cancer (NSCLC) that cannot be removed by surgery and has not worsened after chemoradiation. It is also approved for metastatic NSCLC and small cell lung cancer (SCLC) in both limited and extensive stages.
• Gastrointestinal Cancers: It is approved for use in combination with chemotherapy for locally advanced or metastatic biliary tract cancer and for certain types of resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma.
• Liver Cancer: It is used to treat unresectable hepatocellular carcinoma, often in combination with other medications.
• Bladder Cancer: It is approved for adults with muscle-invasive bladder cancer (MIBC) before and after surgery.

Safety and Monitoring

There are currently no boxed warnings or Risk Evaluation and Mitigation Strategies (REMS) required by the FDA for durvalumab. However, regulatory approval is based on its use under the supervision of healthcare professionals experienced in administering cancer therapies.

FDA-Approved Indications

Durvalumab is approved by the U.S. Food and Drug Administration (FDA) for several types of cancer, often used when the cancer is advanced or has spread.

Lung Cancer

• Non-Small Cell Lung Cancer (NSCLC): Approved for adults with Stage III NSCLC that cannot be removed by surgery and has not worsened after treatment with chemotherapy and radiation.
• Small Cell Lung Cancer (SCLC): Approved for use with chemotherapy as a first-line treatment for extensive-stage SCLC. It is also approved for limited-stage SCLC in patients whose disease has not progressed following concurrent chemoradiotherapy.

Digestive and Liver Cancers

• Biliary Tract Cancer: Approved for use with chemotherapy for adults with locally advanced or metastatic biliary tract cancer.
• Liver Cancer: Approved in combination with tremelimumab for adults with unresectable hepatocellular carcinoma.
• Gastric and Gastroesophageal Junction (GEJ) Cancers: Approved for use with chemotherapy before surgery and as a single agent after surgery for adults with resectable gastric or GEJ adenocarcinoma.

Bladder Cancer

Durvalumab is approved for use with chemotherapy before surgery and as a single agent after surgery for adults with muscle-invasive bladder cancer.