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Journal ArticleDOI

Role of osimertinib in the treatment of EGFR-mutation positive non-small-cell lung cancer.

Jennifer W Carlisle, +1 more
- 18 Jan 2019 - 
- Vol. 15, Iss: 8, pp 805-816
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TLDR
Recently, the FLAURA trial showed significantly improved progression-free survival with osimertinib compared with the first generation EGFR tyrosine kinase inhibitors gefitinib or erlotinib; this has led to its approval by US FDA and European Medicines Agency as frontline therapy.
Abstract
Mutations in the EGFR occur in approximately 10-35% of non-small-cell lung cancer (NSCLC) patients. Osimertinib is a third-generation oral small molecule inhibitor of EGFR, active against the common targetable activating EGFR mutations in L858R and exon 19 deletion; it also inhibits the T790M mutation. It was initially developed and approved for the treatment of acquired resistance to EGFR inhibition mediated by the T790M pathway activation. Recently, the FLAURA trial showed significantly improved progression-free survival with osimertinib compared with the first generation EGFR tyrosine kinase inhibitors gefitinib or erlotinib; this has led to its approval by US FDA and European Medicines Agency (EMA) as frontline therapy. Ongoing studies will define the resistance mechanisms to osimertinib, novel combination approaches and role in earlier stages of NSCLC.

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A review on progression of epidermal growth factor receptor (EGFR) inhibitors as an efficient approach in cancer targeted therapy.

TL;DR: The recent advances on the discovery and development of different EGFR inhibitors and the use of various therapeutic strategies such as multi-targeting agents and combination therapies have also been reviewed.
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An update on the immune landscape in lung and head and neck cancers

TL;DR: An overview of the current immune landscape and future directions in lung cancer and HNSCC is provided to provide a plausible biological rationale to expect that pharmacologic activation of the immune system will be effective for early‐stage and smaller tumors.
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NTRK Fusions in Central Nervous System Tumors: A Rare, but Worthy Target

TL;DR: It is expected that detection of NTRK fusions will soon become a mainstay in the diagnostic assessment of CNS tumors, and thus in-depth knowledge regarding this topic is warranted.
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Efficacy and Safety of Epidermal Growth Factor Receptor (EGFR) Inhibitors Plus Antiangiogenic Agents as First-Line Treatments for Patients With Advanced EGFR-Mutated Non-small Cell Lung Cancer: A Meta-Analysis

TL;DR: Erlotinib plus bevacizumab or ramucirumab in EFGR-mutated NSCLC first-line setting yielded remarkable PFS benefits; however, this was accompanied by higher AEs, and epidermal growth factor receptor–TKI plus antiangiogenic agent therapy may be considered a new option for advanced EGFR-mutations patients.
References
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TL;DR: Recent evidence that Bim proteins are regulated by phosphorylation is considered and the kinases responsible, the phosphorylations sites and effect of phosphorylated proteins on Bim protein function are discussed, seeking to resolve some of the contradictions.
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Journal ArticleDOI

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TL;DR: The results strongly suggest that Met amplification identifies a subset of NSCLC likely to respond to new molecular therapies targeting Met, which is implicated in growth, invasion, and metastasis of many tumors includingNSCLC.
Journal ArticleDOI

MCL1 is phosphorylated in the PEST region and stabilized upon ERK activation in viable cells, and at additional sites with cytotoxic okadaic acid or taxol.

TL;DR: A multiple pathway model is presented, which demonstrates that MCL1 can undergo distinct phosphorylation events – mediated through separate signaling processes and involving different target sites – in cells that remain viable in the presence of TPA versus cells destined to die upon exposure to taxol or okadaic acid.
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