Introduction
Atezolizumab is a humanized monoclonal antibody used to prevent the interaction of PD-L1 and PD-1, removing inhibition of immune responses seen in some cancers. This medication is reserved for patients whose tumors express PD-L1, cannot receive platinum based chemotherapy, or whose tumors do not respond to platinum based chemotherapy. Atezolizumab was granted FDA approval on 18 October 2016.
Uses
Atezolizumab is a monoclonal antibody used to treat advanced or metastatic urothelial carcinoma with disease progression during or up to 12 months after platinum-containing chemotherapy.
Atezolizumab is indicated to treat locally or advanced metastatic urothelial carcinoma in patients ineligible for cicplatin-containing chemotherapy with tumors expressing PD-L1, in patients ineligible for cisplatin-containing chemotherapy irrespective of PD-L1, have disease progression following platinum containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant chemotherapy.
Atezolizumab is also indicated first line for non small cell lung cancer in combination with bevacizumab, paclitaxel, and carboplatin with no EGFR or ALK genomic abnormalities. It can be used in patients with disease progression during or after platinum containing chemotherapy even if they have EGFR and ALK abnormalities.
Atezolizumab is indicated in combination with paclitaxel protein-bound to treat locally advanced or metastatic triple negative breast cancer expressing PD-L1.
Finally, atezolizumab is indicated in combination with carboplatin and etoposide as first line treatment for extensive stage small cell lung cancer.
Associated Conditions
Pharmacodynamics
Atezolizumab is a humanized monoclonal antibody used to prevent the interaction of PD-L1 and PD-1, removing inhibition of immune responses seen in some cancers. This drug has a long duration of action as it is usually given every 3-4 weeks. Atezolizumab should not be used in patients with immune mediated penumonitis, hepatitis, colitis, and some endocrinopathies.
Mechanism of Action
Atezolizumab is a humanized IgG antibody that binds PD-L1, preventing its interaction with PD-1 and B7-1. Preventing the interaction of PD-L1 and PD-1 removes inhibition of immune responses such as the anti-tumor immune response but not antibody dependent cellular cytotoxicity.
Absorption
Pharmacokinetic analysis was performed in patients with metastatic urothelial carcinoma. In these patients, the AUC was 2.19-2.73day*µg/mL/mg, the Cmax was 0.27-0.35µg/mL/mg, and the Cmin was 0.004-0.008µg/mL/mg.
Volume of Distribution
The volume of distribution of atezolizumab is 6.91L.
Protein Binding
Monoclonal antibodies are not expected to bind to proteins in plasma they are not designed to target.
Route of Elimination
Atezolizumab is not renally excreted.
Half Life
The half life of atezolizumab is 27 days.
Clearance
The clearance of atezolizumab is 0.200L/day.
Toxicity
Most common adverse reactions (≥ 20% of patients) included: fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, and constipation.
Overdose data for atezolizumab is scarce but the most common adverse reactions are fatigue, nausea, cough, dyspnea, decreased appetite, alopecia, constipation, diarrhea, peripheral neuropathies, anemia, headache, neutropenia, and vomiting.
Food Interactions
No interactions found.
Dosage
- 1200 mg administered by IV infusion every 3 weeks or
- 1680 mg administered by IV infusion every 4 weeks.