Atezolizumab

Atezolizumab, sold under the brand name Tecentriq among others, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma and alveolar soft part sarcoma, but discontinued for use in triple-negative breast cancer (TNBC). It is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1). The most common side effects when used on its own include tiredness, reduced appetite, nausea, vomiting, cough, difficulty breathing, diarrhea, rash, fever, pain in the back, joints, muscles and bones, weakness, itching and urinary tract infection. The most common side effects when used with other cancer medicines include peripheral neuropathy (nerve damage in the hands and feet), nausea, anemia (low red blood cell counts), neutropenia (low white blood cell counts), thrombocytopenia (low platelet counts), rash, tiredness, constipation, reduced appetite, diarrhea, and cough. Atezolizumab was the first PD-L1 inhibitor approved by the US Food and Drug Administration (FDA) for bladder cancer. In the European Union, atezolizumab is the first PD-(L)1 cancer immunotherapy for subcutaneous injection. Atezolizumab is a therapeutic alternative on the World Health Organization's List of Essential Medicines.

Medical uses In the European Union, atezolizumab is indicated for the treatment of urothelial carcinoma, non-small cell lung cancer, small cell lung cancer, hepatocellular carcinoma, and triple-negative breast cancer. It is no longer indicated for triple-negative breast cancer. In the United States, atezolizumab is indicated for the treatment of non-small cell lung cancer, small cell lung cancer, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma. Its indication for urothelial carcinoma was withdrawn in November 2022.

Adverse effects The most common adverse effects in studies were fatigue, decreased appetite, nausea and infections. Urinary tract infection was the most common severe adverse effect.

Pharmacology

Mechanism of action

Atezolizumab blocks the interaction of PD-L1 with programmed cell death protein 1 (PD-1) and CD80 receptors (B7-1Rs). PD-L1 can be highly expressed on certain tumors, which is thought to lead to reduced activation of immune cells (cytotoxic T-cells in particular) that might otherwise recognize and attack the cancer. Inhibition of PD-L1 by atezolizumab can remove this inhibitor effect and thereby engender an anti-tumor response. It is one of several ways to block inhibitory signals related to T-cell activation, a more general strategy known as immune checkpoint inhibition. For some cancers (notably bladder) the probability of benefit is related to PD-L1 expression, but most cancers with PD-L1 expression still do not respond, and many (about 15%) without PD-L1 expression do respond.

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