Atezolizumab

• Non-Small Cell Lung Cancer (NSCLC):
• Treatment of metastatic NSCLC either as monotherapy in PD-L1 positive tumors or in combination with chemotherapy in selected patients.
• Small Cell Lung Cancer (SCLC):
• First-line treatment of extensive-stage SCLC in combination with chemotherapy.
• Urothelial Carcinoma:
• Treatment of locally advanced or metastatic urothelial carcinoma in patients who are cisplatin-ineligible or after progression following platinum-containing chemotherapy.
• Triple-Negative Breast Cancer (TNBC):
• In combination with nab-paclitaxel for PD-L1 positive unresectable locally advanced or metastatic TNBC.
• Other:
• Investigational uses and clinical trials ongoing for other solid tumors including hepatocellular carcinoma and colorectal cancer.

• Adults:
• Standard dose: 1200 mg administered intravenously over 60 minutes every 3 weeks.
• Dose adjustments based on tolerance and toxicity may be necessary; no dose escalation recommended.
• Pediatrics:
• Safety and efficacy not established.
• Elderly:
• No specific dose adjustments recommended; monitor closely for adverse effects.
• Hepatic/Renal Impairment:
• No dose adjustments required in mild to moderate impairment; severe impairment data limited — monitor carefully.
• Administration:
• Intravenous infusion over 60 minutes; reduce infusion rate in case of infusion-related reactions.
• Pre-medication generally not required but monitor during infusion.

Atezolizumab is a humanized monoclonal antibody targeting programmed death-ligand 1 (PD-L1). By binding PD-L1, it blocks its interaction with PD-1 and B7.1 receptors on T-cells and antigen-presenting cells. This blockade releases PD-L1-mediated inhibition of the immune response, restoring T-cell mediated anti-tumor activity, thereby enhancing the immune system’s ability to detect and destroy cancer cells.

• Absorption: Administered intravenously; bioavailability is 100%.
• Distribution: Volume of distribution approximately 6.9 L, mainly plasma and extracellular fluid.
• Metabolism: Catabolized via non-specific protein degradation pathways to small peptides and amino acids; not metabolized by CYP450 enzymes.
• Half-life: Approximately 27 days, supporting dosing every 2–3 weeks.
• Elimination: Clearance decreases over time with repeated dosing due to target-mediated drug disposition.

• Pregnancy:
• No adequate human data; animal studies show potential fetal risk. Use only if clearly needed and benefits outweigh risks.
• Lactation:
• Unknown if excreted in human milk; potential for immunomodulatory effects in infants. Breastfeeding not recommended during treatment and for 5 months after last dose.

• Immune checkpoint inhibitor
• Anti-PD-L1 monoclonal antibody
• Antineoplastic agent

• Known hypersensitivity to atezolizumab or any excipients.
• Active autoimmune disease requiring systemic immunosuppressive therapy.
• Severe infusion-related reactions to previous administration.

• Immune-mediated adverse reactions including pneumonitis, colitis, hepatitis, endocrinopathies (e.g., thyroiditis, adrenal insufficiency), nephritis, and rash.
• Monitor for symptoms and perform laboratory tests regularly.
• Severe or fatal immune-mediated reactions have occurred; withhold or discontinue drug as per severity.
• Infusion-related reactions: monitor during and after infusion; treat symptoms promptly.
• Increased risk of infections due to immune modulation.
• Caution in patients with preexisting autoimmune disorders.

• Common: Fatigue, nausea, decreased appetite, rash, diarrhea, pyrexia.
• Immune-mediated: Pneumonitis, colitis, hepatitis, endocrinopathies (hypothyroidism, hyperthyroidism, adrenal insufficiency), nephritis.
• Infusion reactions: Fever, chills, hypotension, dyspnea.
• Serious but rare: Severe immune-related adverse events, including neurologic toxicity, myocarditis.

• No significant CYP450 interactions.
• Immunosuppressive agents (e.g., corticosteroids) may reduce atezolizumab efficacy; avoid unless treating immune-related adverse events.
• Live vaccines should be avoided during and after treatment due to immunomodulation.
• No known significant food or alcohol interactions.

• FDA and EMA have expanded indications to include combinations with chemotherapy in lung and breast cancers.
• Updated warnings emphasize early recognition and management of immune-related adverse effects.
• Guidelines recommend regular monitoring of organ function tests and endocrine panels.
• Use in combination regimens is increasing as standard of care in multiple cancers.

• Store vials refrigerated at 2°C to 8°C (36°F to 46°F).
• Do not freeze or shake.
• Protect from light.
• Use immediately after reconstitution or store diluted infusion solution at 2°C to 8°C and use within 24 hours.