Atezolizumab Immunotherapy (TECENTRIQ) for Metastatic Urothelia Carcinoma & Metastatic Non-Small Cell Lung cancer

Atezolizumab is a checkpoint inhibiting immunotherapy

Atezolizumab is an Fc-engineered, humanized, monoclonal antibody that binds to PD-L1 and blocks interactions with the PD-1 and B7.1 receptors. Atezolizumab is a non-glycosylated IgG1 kappa immunoglobulin that has a calculated molecular mass of 145 kDa.

Indication of Atezolizumab (TECENTRIQ)

TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody indicated for the treatment of patients with: 

Advanced or metastatic urothelial carcinoma: Locally advanced or metastatic urothelial carcinoma who: 

• have disease progression during or following platinum-containing chemotherapy.
• have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. 

Metastatic non-small cell lung cancer: who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving TECENTRIQ

Atezolizumab Warning & Precautions

Immune-Related Pneumonitis: Withhold for moderate and permanently discontinue for severe or life-threatening pneumonitis. 

Immune-Related Hepatitis: Monitor for changes in liver function. Withhold for moderate and permanently discontinue for severe or life-threatening transaminase or total bilirubin elevation.

Immune-Related Colitis: Withhold for moderate or severe, and permanently discontinue for life-threatening colitis. 

Immune-Related Endocrinopathies 

 Hypophysitis: Withhold for moderate or severe and permanently discontinue for life-threatening hypophysitis. 

Thyroid Disorders: Monitor for changes in thyroid function. Withhold for symptomatic thyroid disease. 

 Adrenal Insufficiency: Withhold for symptomatic adrenal insufficiency. 

 Type 1 Diabetes Mellitus: Withhold for ≥ Grade 3 hyperglycemia. 

Immune-Related Myasthenic Syndrome/Myasthenia Gravis, GuillainBarré or Meningoencephalitis: Permanently discontinue for any grade.  

 Ocular Inflammatory Toxicity: Withhold for moderate and permanently discontinue for severe ocular inflammatory toxicity. Immune-Related Pancreatitis: Withhold for moderate or severe, and permanently discontinue for life-threatening pancreatitis, or any grade of recurring pancreatitis. 

Infection: Withhold for severe or life-threatening infection. 

Infusion Reaction: Interrupt or slow the rate of infusion for mild or moderate infusion reactions and discontinue for severe or lifethreatening infusion reactions. 

Embryo-Fetal Toxicity: TECENTRIQ can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception.  

Atezolizumab Side Effects/ Adverse Reaction

Most common adverse reactions (≥ 20%) in patients with locally advanced or metastatic urothelial carcinoma were fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, and constipation. (6.1) Most common adverse reactions (≥ 20%) in patients with metastatic non-small cell lung cancer were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation. (6.1)

Formulation of  Atezolizumab/TECENTRIQ 

TECENTRIQ injection for intravenous infusion is a sterile, preservative-free, colorless to slightly yellow solution in single-dose vials. Each mL of TECENTRIQ contains 60 mg of atezolizumab and is formulated in glacial acetic acid (16.5 mg), L-histidine (62 mg), sucrose (821.6 mg), polysorbate 20 (8 mg), pH 5.8. 

Mechanism of Action of Atezolizumab/TECENTRIQ 

 PD-L1 may be expressed on tumor cells and/or tumor-infiltrating immune cells and can contribute to the inhibition of the anti-tumor immune response in the tumor microenvironment. Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation and cytokine production. Atezolizumab is a monoclonal antibody that binds to PD-L1 and blocks its interactions with both PD-1 and B7.1 receptors. This releases the PD-L1/PD-1 mediated inhibition of the immune response, including activation of the anti-tumor immune response without inducing antibodydependent cellular cytotoxicity. In syngeneic mouse tumor models, blocking PD-L1 activity resulted in decreased tumor growth. 12.3 

Pharmacokinetics of Atezolizumab

Patients’ exposures to atezolizumab increased dose proportionally over the dose range of 1 mg/kg to 20 mg/kg, including the fixed dose 1200 mg administered every 3 weeks. Based on a population analysis that included 472 patients in the dose range, the typical population clearance was 0.20 L/day, volume of distribution at steady state was 6.9 L, and the terminal half-life was 27 days. 

The population PK analysis suggests steady state is obtained after 6 to 9 weeks (2 to 3 cycles) of repeated dosing. The systemic accumulation in area under the curve (AUC), maximum concentration (Cmax) and trough concentration (Cmin) was 1.91, 1.46 and 2.75-fold, respectively.

 In a posthoc analysis, atezolizumab clearance was found to decrease over time, with a mean maximal reduction (% coefficient of variation [CV%]) from baseline value of approximately 17.1% (40.6%). However, the decrease in CL was not considered clinically relevant.