Tecentriq

Lung Cancer

Tecentriq is used to treat two main types of lung cancer:

• Non-small cell lung cancer (NSCLC): It may be used as a treatment after surgery and chemotherapy for early-stage cancer (adjuvant treatment), or as a primary treatment for advanced or metastatic NSCLC that has spread to other parts of the body.
• Small cell lung cancer (SCLC): It is used in combination with chemotherapy as a first-line treatment for extensive-stage SCLC.

Liver Cancer

This medication is used to treat hepatocellular carcinoma, the most common type of liver cancer, when it has spread or cannot be removed by surgery. In these cases, it is typically used in combination with another drug called bevacizumab.

Skin Cancer

Tecentriq is used to treat a specific type of skin cancer called melanoma. It is prescribed for melanoma that has spread or cannot be removed by surgery and carries a specific BRAF V600 genetic mutation. For this condition, it is used alongside other medications.

Soft Tissue Cancer

It is approved for the treatment of adults and children 2 years of age and older with a rare type of cancer called alveolar soft part sarcoma (ASPS) when the cancer has spread or cannot be removed by surgery.

The Immune System and Cancer

The immune system uses specialized white blood cells called T-cells to protect the body from infections and abnormal cells, including cancer. However, some cancer cells develop ways to hide from these T-cells to avoid being destroyed.

How Tecentriq Works

Tecentriq (atezolizumab) is a monoclonal antibody that targets a specific protein called programmed death-ligand 1 (PD-L1). This protein can be found on the surface of some cancer cells and certain immune cells.

When PD-L1 binds to other proteins (PD-1 and B7.1) on the surface of T-cells, it acts like a brake, sending a signal that tells the T-cell not to attack. Tecentriq works by:

• Blocking the PD-L1 protein: By attaching to PD-L1, the drug prevents it from connecting with the receptors on T-cells.
• Releasing the brakes: Once the interaction is blocked, the immune system's brakes are released.
• Activating T-cells: This allows the T-cells to recognize the cancer cells as a threat and begin attacking them.

Because Tecentriq works with the immune system rather than attacking the cancer directly, it is classified as an immunotherapy or a checkpoint inhibitor.

Common Side Effects

The most common side effects reported by people taking Tecentriq include:

• Fatigue and weakness
• Nausea and vomiting
• Decreased appetite
• Constipation or diarrhea
• Cough and shortness of breath
• Rash and itchy skin
• Fever
• Muscle, joint, or bone pain
• Urinary tract infections

Serious Side Effects

Tecentriq works by stimulating the immune system, which can sometimes cause it to attack normal, healthy tissues. These immune-mediated reactions can be severe or life-threatening and may occur in various parts of the body during or after treatment:

• Lung problems: Inflammation of the lungs (pneumonitis) which can cause new or worsening cough, chest pain, or shortness of breath.
• Liver problems: Inflammation of the liver (hepatitis) which may cause yellowing of the skin or eyes (jaundice), dark urine, or pain on the right side of the stomach area.
• Intestinal problems: Inflammation of the colon (colitis) that can lead to severe diarrhea, stomach pain, or stools that are black, tarry, or contain blood.
• Hormone gland problems: Issues with the thyroid, adrenal, or pituitary glands, or the development of type 1 diabetes. Symptoms may include extreme tiredness, weight changes, or increased thirst.
• Kidney problems: Inflammation of the kidneys (nephritis) which can cause changes in the amount or color of urine, or swelling in the ankles.
• Severe skin reactions: Rashes that may blister or peel, which can be life-threatening.
• Infusion-related reactions: Symptoms like chills, shaking, dizziness, flushing, or fever that occur during or shortly after the medication is administered.

Contact a healthcare provider immediately if you experience any new or worsening symptoms while receiving this treatment.

Immune-Mediated Adverse Reactions

Tecentriq is an immunotherapy that works by helping the immune system attack cancer cells. However, it can also cause the immune system to attack healthy organs and tissues in any part of the body. These reactions can occur at any time during treatment or even after treatment has stopped. Serious or fatal reactions may involve the following:

• Lungs: Inflammation of the lungs (pneumonitis) which can cause shortness of breath, chest pain, or a new or worsening cough.
• Intestines: Inflammation of the colon (colitis) resulting in diarrhea, blood in the stool, or severe stomach pain.
• Liver: Inflammation of the liver (hepatitis) which may lead to yellowing of the skin or eyes (jaundice), dark urine, or severe nausea and vomiting.
• Hormone Glands: Problems with the thyroid, adrenal glands, pituitary gland, or pancreas (including type 1 diabetes). Symptoms may include extreme tiredness, weight changes, or increased thirst and urination.
• Kidneys: Inflammation of the kidneys (nephritis) which can affect kidney function and cause changes in the amount or color of urine.
• Skin: Severe skin reactions, including rashes, itching, blistering, or peeling.

Infusion-Related Reactions

Severe or life-threatening reactions can occur during the administration of the medication. Medical staff monitor for these reactions during and after the infusion. Symptoms may include chills, shaking, dizziness, itching, rash, fever, or difficulty breathing.

Embryo-Fetal Toxicity

Tecentriq can cause harm to a fetus if administered during pregnancy. Females of reproductive potential are typically advised to use effective contraception during treatment and for at least five months after the final dose. Breastfeeding is generally not recommended during treatment and for five months following the last dose due to the potential for serious adverse reactions in the infant.

Complications of Stem Cell Transplant

Serious and potentially fatal complications can occur in patients who receive an allogeneic hematopoietic stem cell transplant (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody like Tecentriq. These complications may include severe graft-versus-host disease (GVHD).

Monitoring

Healthcare providers perform regular blood tests to monitor liver function, kidney function, thyroid levels, and blood glucose levels. This monitoring helps detect early signs of immune-mediated reactions before they become severe.

Pregnancy

Tecentriq can cause fetal harm when administered to a pregnant woman. Based on how the drug works, it may cause the mother's immune system to respond against the developing fetus, which could lead to pregnancy loss or fetal death. Animal studies have shown that similar medications increase the risk of spontaneous abortion.

Healthcare providers typically require a pregnancy test before starting treatment for individuals who can become pregnant. If you are pregnant or planning to become pregnant, it is important to discuss the potential risks to the fetus with your medical team.

Contraception: Individuals of reproductive potential are advised to use effective birth control during treatment with Tecentriq and for at least 5 months after the final dose.

Breastfeeding

It is not known if Tecentriq passes into human breast milk. Because of the potential for serious adverse reactions in a nursing infant, manufacturers recommend that individuals do not breastfeed during treatment and for at least 5 months after the last dose. You should discuss feeding options with your healthcare provider to determine the safest approach for your situation.

Available Forms

Tecentriq is supplied as a sterile, preservative-free solution for administration by a healthcare professional. It is available in the following form:

• Intravenous Injection: A clear, colorless to slightly yellow liquid solution provided in single-dose vials. This medication is intended for dilution and administration as an infusion into a vein.

FDA Approval and Indications

Tecentriq is a programmed death-ligand 1 (PD-L1) blocking antibody. It is approved by the U.S. Food and Drug Administration (FDA) for the treatment of several malignancies, often depending on specific genetic markers or the stage of the disease. Key approved uses include:

• Non-Small Cell Lung Cancer (NSCLC): Approved as an adjuvant treatment following surgery and platinum-based chemotherapy for adults with Stage II to IIIA NSCLC whose tumors have PD-L1 expression on 1% or more of tumor cells. It is also approved for the first-line treatment of metastatic NSCLC in patients with high PD-L1 expression and no EGFR or ALK genomic tumor aberrations.
• Small Cell Lung Cancer (SCLC): Approved for use in combination with carboplatin and etoposide for the first-line treatment of adults with extensive-stage SCLC.
• Hepatocellular Carcinoma (HCC): Approved in combination with bevacizumab for patients with unresectable or metastatic HCC who have not received prior systemic therapy.
• Melanoma: Approved in combination with cobimetinib and vemurafenib for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.

Regulatory History and Safety

The regulatory status of Tecentriq has evolved over time. Some indications that received accelerated approval, such as for certain types of urothelial (bladder) cancer, were later voluntarily withdrawn by the manufacturer after confirmatory trials did not meet their primary endpoints.

There are currently no boxed warnings or Risk Evaluation and Mitigation Strategy (REMS) requirements for Tecentriq. However, the FDA monitors the drug for immune-related adverse reactions, which are a known risk with this class of immunotherapy.

Initial and Subsequent Approvals

Tecentriq first received FDA approval in 2016. Since then, its approved uses have expanded to include various stages and types of cancer, often used when the cancer has spread or cannot be removed by surgery.

Approved Indications

The FDA has approved Tecentriq for the following conditions:

• Non-Small Cell Lung Cancer (NSCLC): Used as a standalone treatment, in combination with other therapies, or as an adjuvant treatment after surgery and chemotherapy for certain patients.
• Small Cell Lung Cancer (SCLC): Used in combination with chemotherapy as a first-line treatment for extensive-stage disease.
• Hepatocellular Carcinoma: Used in combination with bevacizumab for patients with liver cancer that has spread or cannot be removed by surgery.
• Melanoma: Used in combination with cobimetinib and vemurafenib for certain types of advanced skin cancer.
• Alveolar Soft Part Sarcoma: Approved for adults and children 2 years of age and older with this rare type of cancer.

Some approvals were granted under the FDA's accelerated approval program, which allows for earlier access to medications that treat serious conditions based on promising initial data, though continued approval may depend on further clinical trials.