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Atezolizumab (Tecentriq®)

Mann, Janelle E. PHARMD, BCOP

doi: 10.1097/01.COT.0000513325.52233.f1
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What is atezolizumab?

Atezolizumab is a programmed death-ligand (PD-L1) blocking humanized, monoclonal antibody.

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How does atezolizumab work?

PD-L1 is expressed on tumor cells and tumor-infiltrating immune cells. The binding of PD-L1 to PD-1 and B7.1 receptors on T cells can lead to the inhibition of cytotoxic activity, proliferation, and cytokine production of the T cell within the tumor microenvironment. Atezolizumab binds to PD-L1, inhibits the interaction with PD-1 and B7.1 receptors, and allows for activation of anti-tumor immune responses.

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What is this approved for?

Atezolizumab was initially approved for locally advanced or metastatic urothelial carcinoma after progression following platinum-containing chemotherapy or progression within 12 months of neoadjuvant or adjuvant treatment with a platinum-containing agent. In October 2016, the FDA approved atezolizumab for the treatment of metastatic non-small cell lung cancer (NSCLC) in patients who have disease progression during or following platinum-containing chemotherapy, or patients with EGFR or ALK genomic alterations who have failed approved targeted therapies.

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What is the basis for this approval?

Atezolizumab was granted FDA approval based on two international, randomized, open-label randomized phase II (POPLAR) and phase III (OAK) clinical trials where patients with metastatic NSCLC who progressed on post-platinum chemotherapy were randomized to atezolizumab or docetaxel. Each study randomized patients to either atezolizumab 1,200 mg IV or docetaxel 75 mg/m2 IV every 3 weeks until disease progression. The results of the OAK trial showed superiority of atezolizumab compared to docetaxel with the median overall survival of 13.8 months with atezolizumab versus 9.6 months with docetaxel (p=0.0003) (Lancet 2016;389:255-265). Both studies found patients with high expression of PDL-1 had greater responses.

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How do you administer this drug?

Atezolizumab is administered as a 1,200 mg flat dose intravenously over 60 minutes every 3 weeks until disease progression or toxicity. If the first infusion is tolerated, then subsequent doses can be administered over 30 minutes.

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Are there any premedications needed?

None required.

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What are the common side effects associated with atezolizumab (> or =10%)?

Atezolizumab resulted in the following adverse effects (NSCLC):

  • General: fatigue, musculoskeletal pain
  • GI: decreased appetite, nausea, constipation
  • Lung: dyspnea, cough
  • Laboratory: hyponatremia, hypoalbuminemia, elevated transaminases, hypokalemia, hypercalcemia, hyperbilirubinemia
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What are the uncommon side effects associated with atezolizumab (less than 10%)?

About 2 percent of patients with NSCLC developed a severe infusion reaction from atezolizumab. Immune-mediated reactions have been observed with pneumonitis occurring in 3.7 percent of patients. Infection rates were greater with atezolizumab when compared to docetaxel for NSCLC with 7.7 percent of patients experiencing grade 3 or higher infections with pneumonia.

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Are there any important drug interactions I should be aware of?

No known drug interactions.

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How do I adjust the dose in the setting of renal or hepatic insufficiency?

There are no dose adjustment recommendations for renal or hepatic insufficiencies. Atezolizumab has not been studied in patients with severe renal impairment or moderate to severe hepatic impairment; however, drug exposure is not expected to be different as pharmacokinetically, atezolizumab is not hepatically metabolized or renally excreted.

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Practical tips

Clinically significant immune-related adverse effects were observed with atezolizumab, which included pneumonitis, hepatitis, colitis, and thyroid disease. Early detection and management with corticosteroids for immune-mediated reactions is key. Infusion reactions have been observed and it is recommended to interrupt or slow the rate of infusion in patients with mild to moderate reactions. Severe infusion reactions require permanent discontinuation of atezolizumab.

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What should my patients know about atezolizumab?

Patients should contact their health care provider if they experience any of the following:

  • Itching, shortness of breath, or flushing during the infusion
  • Fever
  • New or worsening cough, shortness of breath, or chest pain
  • Yellowing of skin or the whites of the eyes, abdominal pain, dark urine
  • Diarrhea, blood in the stools, severe abdominal pain or tenderness
  • Nausea or vomiting that is uncontrolled with medications at home
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What else should I know about atezolizumab?

Patients were excluded who had a history of autoimmune disease; active or corticosteroid-dependent brain metastases; received a live, attenuated vaccine within 28 days prior to enrollment; received a systemic immunostimulatory agent within 4 weeks or systemic immunosuppressive medication within 2 weeks prior to enrollment.

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What useful links are available regarding atezolizumab?

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Any ongoing clinical trials related to atezolizumab?

Clinical trials with atezolizumab are being conducted in the first-line setting for metastatic NSCLC in combination with chemotherapy, metastatic urothelial or non-urothelial carcinoma, induction therapy for early stage NSCLC, and in advanced solid tumors. More information is available about the clinical trials at https://clinicaltrials.gov.

JANELLE E. MANN, PHARMD, BCOP, is an Investigational Drug Pharmacist, Washington University School of Medicine, Alvin J. Siteman Cancer Center, St. Louis, Mo., and also serves as the Pharmacy Forum column co-editor. Oncology Times Clinical Advisory Editor RAMASWAMY GOVINDAN, MD, Co-Director, Section of Medical Oncology, Professor of Medicine, Washington University School of Medicine, Alvin J. Siteman Cancer Center, serves as the Pharmacy Forum column physician advisor.

Janelle E. Mann, PHARMD, BCOP

Janelle E. Mann, PHARMD, BCOP

Ramaswamy Govindan, MD

Ramaswamy Govindan, MD

Wolters Kluwer Health, Inc. All rights reserved.
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