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Atezolizumab: Mechanism of Action, Adverse Effects, Contraindications and Dosage
Mechanism of action of atezolizumab:
Atezolizumab is a monoclonal antibody against PD-L1, a ligand of the PD-1 receptor. By blocking PD-L1, it releases an immune-checkpoint brake and thereby strengthens the cellular immune response against metastatic tumors.
Urologic indications of atezolizumab:
Atezolizumab is authorized in Europe as monotherapy for metastatic urothelial carcinoma in the following situations:
- Second-line therapy after progression on platinum-based chemotherapy: the objective response rate was 15%, including 5% complete responses (Rosenberg et al., 2016). Higher PD-L1 expression correlated with higher response rates. Atezolizumab showed better tolerability than investigator’s-choice second-line chemotherapy with vinflunine, paclitaxel, or docetaxel (Powles et al., 2017). In contrast to the USA, atezolizumab received approval in Europe, although the phase 3 trial did not demonstrate an overall-survival benefit.
- First-line therapy for cisplatin-ineligible patients with PD-L1 ≥5.
Pharmacokinetics of atezolizumab:
Intravenous administration over one hour. Elimination half-life is approximately 27 days. Catabolism through proteolytic pathways.
Adverse effects of Atezolizumab:
Atezolizumab is associated with immune-mediated adverse events that may occur up to five months after the last dose. Depending on severity, clinicians should hold or discontinue pembrolizumab and initiate corticosteroids (typically methylprednisolone 1–3 mg/kg/day), followed by an appropriate taper. See the section on adverse effects of immune checkpoint inhibition for each organ system.
Contraindications of Atezolizumab:
Pregnancy and breastfeeding. Loss of clinical benefit or unequivocal disease progression. Immune-mediated adverse effects of grade 4; persistent grade 2/3 adverse effects despite treatment interruption and corticosteroids.
Drug Interactions of Atezolizumab:
Systemic corticosteroids and other immunosuppressants may blunt the pharmacodynamic activity of atezolizumab and should be avoided unless clinically necessary to manage immune-mediated toxicity. Live vaccines are generally not recommended during treatment.
There is a complex interplay between the gut microbiome and checkpoint inhibitor activity. Prior or early exposure to systemic antibiotics has been associated with reduced efficacy in observational studies.
Dosage of Atezolizumab:
Current labels allow multiple fixed IV schedules: 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks. Administer as an intravenous infusion over 60 minutes.
Monitoring During Therapy:
Before each treatment cycle of atezolizumab, assess for symptoms and laboratory abnormalities. Provide thorough patient education and perform targeted review of systems across all organ systems to ensure prompt diagnostics, treatment pause or discontinuation, and timely steroid initiation when indicated.
- Thorough medical history and physical examination: Inspect skin and oral mucosa; auscultate lungs; perform a focused neurologic examination; measure the blood pressure.
- Laboratory monitoring: Complete blood count with differential; electrolytes; liver function tests and bilirubin; lipase; creatine kinase and troponin; coagulation studies; blood glucose; creatinine; TSH and free T4; LDH; CRP.
Urologic drugs | Index | Ipilimumab |
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References
T. Powles and Durà, “Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomized controlled trial.” Lancet, 2017.
J. E. Rosenberg et al., “Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial.” Lancet 2016;387:1909–1920.
Deutsche Version: Atezolizumab
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