Atezolizumab

Usage

Atezolizumab is prescribed for the treatment of various types of cancers, including:

• Urothelial Carcinoma: Locally advanced or metastatic urothelial carcinoma (bladder cancer) in patients who are not eligible for cisplatin-containing chemotherapy or whose disease has progressed during or after platinum-containing chemotherapy.
• Non-Small Cell Lung Cancer (NSCLC): Metastatic NSCLC in patients whose tumors have PD-L1 expression ≥ 1% and who have progressed during or after platinum-containing chemotherapy. Also used as adjuvant treatment after resection and platinum-based chemotherapy in adults with stage II-IIIA NSCLC whose tumors have PD-L1 expression ≥1%.
• Small Cell Lung Cancer (SCLC): Extensive-stage SCLC in combination with carboplatin and etoposide.
• Triple-Negative Breast Cancer (TNBC): PD-L1-positive, unresectable, locally advanced, or metastatic TNBC in combination with paclitaxel protein-bound.
• Hepatocellular Carcinoma (HCC): Unresectable HCC in combination with bevacizumab.
• Melanoma: Unresectable or metastatic melanoma in combination with cobimetinib and vemurafenib.
• Alveolar Soft Part Sarcoma (ASPS): For patients 2 years and older.

Pharmacological Classification: Atezolizumab is a monoclonal antibody classified as an immune checkpoint inhibitor.

Mechanism of Action: Atezolizumab targets and binds to Programmed Death-Ligand 1 (PD-L1), a protein found on some tumor cells and tumor-infiltrating immune cells. By blocking PD-L1, atezolizumab prevents it from interacting with the PD-1 and B7.1 receptors on T-cells. This blockade releases the PD-L1/PD-1 pathway-mediated suppression of the immune system, allowing T-cells to recognize and attack cancer cells.

Alternate Names

International Nonproprietary Name (INN): atezolizumab

Brand Name: Tecentriq, Tecentriq Hybreza (in combination with hyaluronidase-tqjs for subcutaneous injection)

How It Works

Pharmacodynamics: Atezolizumab enhances T-cell activation and antitumor immune responses by binding to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, preventing its interaction with PD-1 and B7-1 receptors.

Pharmacokinetics:

• Absorption: Administered intravenously or subcutaneously. Bioavailability is 100% for intravenous administration.
• Distribution: Follows a linear, two-compartment disposition model. Volume of distribution at steady state is approximately 6.9 L.
• Metabolism: Primarily cleared by catabolism, similar to endogenous IgG antibodies. No metabolic drug-drug interactions expected.
• Elimination: Terminal half-life is around 27 days. Clearance is approximately 0.2 L/day.

Mode of Action: Atezolizumab acts by binding to PD-L1, thereby blocking the interaction between PD-L1 and its receptors, PD-1 and B7.1, on T-cells. This inhibition releases the “brakes” on the immune system, enabling T-cells to effectively target and destroy cancer cells.

Receptor Binding: Binds to the PD-L1 receptor.

Elimination Pathways: Primarily eliminated through catabolism (breakdown into smaller peptides and amino acids).

Dosage

Standard Dosage

Adults:

• Intravenous Infusion: 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks.
• Subcutaneous Injection (Tecentriq Hybreza): 1680 mg every 4 weeks.

Children (ASPS, age 2 years and older):

• 15 mg/kg (maximum 1200 mg) intravenously every 3 weeks.

Special Cases:

• Elderly Patients: No dose adjustment required.
• Patients with Renal Impairment: No dose adjustment required.
• Patients with Hepatic Dysfunction: No dose adjustment required.
• Patients with Comorbid Conditions: Dose adjustments may be necessary depending on specific comorbidities and their severity. Consult product monograph for detailed guidance.

Clinical Use Cases

Dosage and administration are the same across various clinical settings, including intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations. The specific indication determines the appropriate combination therapy (e.g., with bevacizumab for HCC).

Dosage Adjustments

Dosage adjustments may be needed for patients experiencing immune-related adverse events. See the Side Effects section and consult the full prescribing information for details on managing these events.

Side Effects

Common Side Effects:

Fatigue, decreased appetite, nausea, diarrhea, cough, rash, itching, musculoskeletal pain, infusion-related reactions.

Rare but Serious Side Effects:

Pneumonitis, colitis, hepatitis, endocrinopathies (thyroid dysfunction, adrenal insufficiency, type 1 diabetes mellitus, hypophysitis), nephritis, skin reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis), neurological complications (Guillain-Barré syndrome, myasthenia gravis), infusion reactions.

Long-Term Effects: Potential long-term effects may include persistent fatigue, organ damage from immune-related adverse events, and secondary malignancies.

Adverse Drug Reactions (ADR): Immune-mediated adverse reactions are serious and can be life-threatening. They require prompt recognition, evaluation, and management.

Contraindications

Known hypersensitivity to atezolizumab or any component of the formulation.

Drug Interactions

No formal drug interaction studies have been conducted. Systemic corticosteroids or immunosuppressants should be avoided before starting atezolizumab but can be used to manage immune-related adverse events after treatment initiation. Consult the full prescribing information for a detailed assessment of potential drug interactions.

Pregnancy and Breastfeeding

Pregnancy: Atezolizumab can cause fetal harm. Women of childbearing potential should use effective contraception during treatment and for at least 5 months after the last dose.

Breastfeeding: Breastfeeding is not recommended during treatment and for at least 5 months after the last dose.

Drug Profile Summary

• Mechanism of Action: PD-L1 inhibitor, enhances T-cell activation.
• Side Effects: Fatigue, decreased appetite, infusion reactions; serious immune-related adverse events (pneumonitis, colitis, hepatitis, endocrinopathies).
• Contraindications: Hypersensitivity to atezolizumab.
• Drug Interactions: Avoid systemic corticosteroids/immunosuppressants before initiating therapy.
• Pregnancy & Breastfeeding: Contraindicated in pregnancy, avoid breastfeeding.
• Dosage: IV: 840 mg q2w, 1200 mg q3w, or 1680 mg q4w; SC: 1680 mg q4w. Pediatrics (ASPS): 15 mg/kg (max 1200 mg) IV q3w.
• Monitoring Parameters: Monitor for immune-related adverse events (organ function tests, clinical signs/symptoms), complete blood counts.

Popular Combinations

• Bevacizumab: For hepatocellular carcinoma.
• Carboplatin and Etoposide: For small cell lung cancer.
• Cobimetinib and Vemurafenib: For melanoma.
• Paclitaxel protein-bound: For triple-negative breast cancer.

Precautions

• General Precautions: Monitor for immune-related adverse events. Evaluate for infections.
• Pregnant Women: Avoid use.
• Breastfeeding Mothers: Avoid use.
• Children & Elderly: No specific dose adjustments but monitor for adverse events.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Atezolizumab?

A: Adults: 840 mg IV q2w, 1200 mg IV q3w, or 1680 mg IV q4w; 1680 mg SC q4w. Pediatrics (ASPS, age 2+): 15 mg/kg (max 1200 mg) IV q3w.

Q2: What are the most common side effects?

A: Fatigue, decreased appetite, nausea, diarrhea, cough, rash, itching, musculoskeletal pain.

Q3: What are the serious immune-related adverse events associated with atezolizumab?

A: Pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, skin reactions (including SJS/TEN), neurological complications.

Q4: How should immune-related adverse events be managed?

A: Requires prompt evaluation and management, including withholding atezolizumab and administering corticosteroids. Consult the full prescribing information for specific guidelines.

Q5: Can atezolizumab be used during pregnancy or breastfeeding?

A: No, atezolizumab can cause fetal harm and is not recommended during pregnancy or breastfeeding.

Q6: What is the mechanism of action of atezolizumab?

A: It’s a PD-L1 inhibitor that blocks the PD-1/PD-L1 pathway, enhancing T-cell activation and the anti-tumor immune response.

Q7: Are there any specific drug interactions to be aware of?

A: Avoid systemic corticosteroids or immunosuppressants before starting atezolizumab. Consult the full prescribing information for a comprehensive list of drug interactions.

Q8: How is atezolizumab administered?

A: Intravenous infusion or subcutaneous injection (Tecentriq Hybreza).

Q9: What are the key monitoring parameters for patients receiving atezolizumab?

A: Monitor for immune-related adverse events through clinical assessment, organ function tests, and complete blood counts.

This information is current as of February 16, 2025, and may change as new research emerges. Please always consult the most up-to-date prescribing information before making treatment decisions.