Atezolizumab (trade name Tecentriq) is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1).
In 2015, it was in clinical trials as an immunotherapy for several types of solid tumors. It was under investigation by Genentech/Roche.
In April 2016, Roche announced that atezolizumab had been granted fast track status for lung cancer by the FDA.
In May 2016, it was approved by the FDA for bladder cancer treatment., but in May 2017 it failed phase 3 trial for second line bladder cancer.
In May 2018, Tecentriq was in combination with Avastin and standard chemotherapy for some patients with lung cancer was granted priority review. A decision by the U.S. Food and Drug Administration is expected by 5 September 2018.
Video Atezolizumab
Medical uses
In May 2016 FDA granted accelerated approval to atezolizumab for locally advanced or metastatic urothelial carcinoma treatment after failure of cisplatin-based chemotherapy. The confirmatory trial (to convert the accelerated approval into a full approval) failed to achieve its primary endpoint of overall survival.
In October 2016, FDA approved atezolizumab for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose disease progressed 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 atezolizumab.
Maps Atezolizumab
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.
Research
As of 2016, it is currently in clinical trials for colorectal cancer, melanoma, breast cancer, non-small-cell lung carcinoma, bladder cancer, renal cell carcinoma.
Promising results have been observed for melanoma and non-small-cell lung cancer, and bladder cancer.
A phase 1 trial reported a 19% objective response rate in metastatic triple-negative breast cancer.
References
Source of article : Wikipedia
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