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https://www.readbyqxmd.com/read/27923840/osimertinib-for-the-treatment-of-metastatic-epidermal-growth-factor-t970m-positive-non-small-cell-lung-cancer
#1
Sean Khozin, Chana Weinstock, Gideon M Blumenthal, Joyce Cheng, Kun He, Luning Zhuang, Hong Zhao, Rosane Charlab Orbach, Ingrid Fan, Patricia Keegan, Richard Pazdur
On November 13, 2015, FDA granted accelerated approval to osimertinib (TAGRISSO™; AstraZeneca), a breakthrough therapy-designated drug for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, with progression on or after EGFR tyrosine kinase inhibitor therapy. Approval was based on durable tumor response rates in two single-arm, multicenter trials: the dose extension cohort of a first-in-human trial (AURA extension; n=201) and a fixed-dose, activity-estimating trial (AURA2; n=210)...
December 6, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27923714/brief-report-acquired-braf-v600e-mutation-as-resistant-mechanism-after-treatment-with-osimertinib
#2
Chao-Chi Ho, Wei-Yu Liao, Chih-An Lin, Jin-Yuan Shih, Chong-Jen Yu, James Chih-Hsin Yang
INTRODUCTION: AZD9291 (osimertinib) is designed for acquired T790M mutation after first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been used. Some of the resistance mechanisms that present after osimertinib treatment, including a newly acquired EGFR C797S mutation, have been identified. It is unclear, however, whether the bypass pathway is also a resistant mechanism in patients after osimertinib treatment. METHODS: Cells from malignant pleural effusion were collected and cultured at the time of progression in a patient being treated with osimertinib...
December 3, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27912836/epidermal-growth-factor-receptor-mutated-advanced-non-small-cell-lung-cancer-a-changing-treatment-paradigm
#3
REVIEW
Suchita Pakkala, Suresh S Ramalingam
Activating mutations in the epidermal growth factor receptor (EGFR) are present in approximately 15% of US patients with lung adenocarcinoma. EGFR tyrosine kinase inhibitors are associated with high response rate and progression-free survival for patients with non-small cell lung cancer with this genotype. Gefitinib, erlotinib, and afatinib are the EGFR tyrosine kinase inhibitors that are presently in clinical use. Understanding resistance mechanisms has led to the identification of a secondary mutational target, T790M, in more than half of patients, for which osimertinib has been approved...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27912760/update-on-recent-preclinical-and-clinical-studies-of-t790m-mutant-specific-irreversible-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors
#4
REVIEW
Bin-Chi Liao, Chia-Chi Lin, Jih-Hsiang Lee, James Chih-Hsin Yang
The first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (1/2G EGFR-TKIs) gefitinib, erlotinib, and afatinib have all been approved as standard first-line treatments for advanced EGFR mutation-positive non-small cell lung cancer. The third-generation (3G) EGFR-TKIs have been developed to overcome the EGFR T790M mutation, which is the most common mechanism of acquired resistance to 1/2G EGFR-TKI treatment. This resistance mutation develops in half of the patients who respond to 1/2G EGFR-TKI therapy...
December 3, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27910964/osimertinib-a-third-generation-tyrosine-kinase-inhibitor-targeting-non-small-cell-lung-cancer-with-egfr-t790m-mutations
#5
C E McCoach, A Jimeno
Oncogenic driver mutations in the epidermal growth factor receptor (EGFR) gene have provided a focus for effective targeted therapy. Unfortunately, all patients eventually develop resistance to frontline therapy with EGFR tyrosine kinase inhibitors (TKIs). The majority of patients develop a large subclonal population of tumor cells with a T790M mutation that renders these cells resistant to first-generation TKIs. Osimertinib is a third-generation EGFR TKI that was designed to overcome resistance from T790M mutations...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27896061/successful-retreatment-with-osimertinib-after-osimertinib-induced-acute-pulmonary-embolism-in-a-patient-with-lung-adenocarcinoma-a-case-report
#6
Takayuki Shiroyama, Manabu Hayama, Shingo Satoh, Shingo Nasu, Ayako Tanaka, Satomu Morita, Naoko Morishita, Hidekazu Suzuki, Norio Okamoto, Tomonori Hirashima
Pulmonary embolism (PE) can be life-threatening, and it is challenging to diagnose because of its nonspecific signs and symptoms. PE is also an important potential risk of osimertinib treatment, however, clinical courses regarding retreatment after osimertinib-induced acute pulmonary embolism remain unclear. We described a 77-year-old woman with postoperative recurrent lung adenocarcinoma who developed osimertinib-induced acute PE. She received apixaban and was later successfully retreated with osimertinib...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/27885838/osimertinib-for-egfr-t790m-mutation-positive-non-small-cell-lung-cancer
#7
Kenzo Soejima, Hiroyuki Yasuda, Toshiyuki Hirano
Significant advances have been made since the development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFR mutations in non-small-cell lung cancer (NSCLC), however, lung cancer cells eventually acquire resistance to those agents. Osimertinib (AZD9291) has been developed as 3(rd) generation EGFR-TKI with activities against sensitizing mutations and T790 M resistance mutation, which account for about 50% of the mechanisms of acquired resistance to 1(st) or 2(nd) generation EGFR-TKIs...
December 2, 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27866634/transient-asymptomatic-pulmonary-opacities-during-osimertinib-treatment-stop-or-go-decision
#8
EDITORIAL
Myung-Ju Ahn, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park
No abstract text is available yet for this article.
December 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27861144/inhibition-of-oxidative-phosphorylation-suppresses-the-development-of-osimertinib-resistance-in-a-preclinical-model-of-egfr-driven-lung-adenocarcinoma
#9
Matthew J Martin, Cath Eberlein, Molly Taylor, Susan Ashton, David Robinson, Darren Cross
Metabolic plasticity is an emerging hallmark of cancer, and increased glycolysis is often observed in transformed cells. Small molecule inhibitors that target driver oncogenes can potentially inhibit the glycolytic pathway. Osimertinib (AZD9291) is a novel EGFR tyrosine kinase inhibitor (TKI) that is potent and selective for sensitising (EGFRm) and T790M resistance mutations. Clinical studies have shown osimertinib to be efficacious in patients with EGFRm/ T790M advanced NSCLC who have progressed after EGFR-TKI treatment...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27835594/characterization-of-osimertinib-azd9291-resistant-non-small-cell-lung-cancer-nci-h1975-osir-cell-line
#10
Zheng-Hai Tang, Xiao-Ming Jiang, Xia Guo, Chi Man Vivienne Fong, Xiuping Chen, Jin-Jian Lu
Osimertinib (OSI, also known as AZD9291) is the newest FDA-approved epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutation. However, resistance to OSI is likely to progress and the study of potential OSI-resistant mechanisms in advanced is necessary. Here, the OSI-resistant NCI-H1975/OSIR cells were established. After cells developed resistance to OSI, cell proliferation was decreased while cell migration and invasion were increased...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27827863/novel-selective-and-potent-egfr-inhibitor-that-overcomes-t790m-mediated-resistance-in-non-small-cell-lung-cancer
#11
Yanxia Li, Zhendong Song, Yue Jin, Zeyao Tang, Jian Kang, Xiaodong Ma
Treating patients suffering from EGFR mutant non-small cell lung cancer (NSCLC) with first-generation EGFR tyrosine kinase inhibitors (EGFR TKI) provides excellent response rates. However, approximately 60% of all patients ultimately develop drug resistance due to a second T790M EGFR TKI mutation. In this study, we report the novel molecule N-(3-((5-chloro-2-(4-((1-morpholino)methyl)phenylamino)-4-pyrimidinyl)amino)phenyl)acrylamide (DY3002) to preferentially inhibit the EGFR T790M mutant (EGFR(T790M)) (IC50 = 0...
November 2, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27821794/understanding-mechanisms-of-resistance-in-the-epithelial-growth-factor-receptor-in-non-small-cell-lung-cancer-and-the-role-of-biopsy-at-progression
#12
REVIEW
Mark A Socinski, Liza C Villaruz, Jeffrey Ross
: : Molecular profiling and the discovery of drugs that target specific activating mutations have allowed the personalization of treatment for non-small cell lung cancer (NSCLC). The epithelial growth factor receptor (EGFR) is frequently overexpressed and/or aberrantly activated in different cancers, including NSCLC. The most common activating mutations of EGFR in NSCLC fall within the tyrosine kinase-binding domain. Three oral EGFR tyrosine kinase inhibitors (TKIs) have been approved by the U...
November 7, 2016: Oncologist
https://www.readbyqxmd.com/read/27821604/targeting-the-gatekeeper-osimertinib-in-egfr-t790m-mutation-positive-non-small-cell-lung-cancer
#13
Ferdinandos Skoulidis, Vassiliki A Papadimitrakopoulou
In 2015 the FDA approved an unprecedented number of new therapies for non-small cell lung cancer (NSCLC), among them therapies addressing specific genomic tumor subsets in the setting of development of resistance to front-line targeted therapy. Osimertinib (TagrissoTM, AZD9291) is indicated for patients with metastatic EGFR (epidermal growth factor receptor) T790M mutation-positive NSCLC, as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy and received breakthrough therapy designation, priority review status, and accelerated approval...
November 7, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27814987/nice-approves-osimertinib-for-advanced-lung-cancer
#14
Talha Khan Burki
No abstract text is available yet for this article.
November 1, 2016: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/27793811/osimertinib-is-active-in-patients-with-egfrt790m-positive-nsclc
#15
(no author information available yet)
Osimertinib is safe and effective in patients who progressed on an EGFR tyrosine kinase inhibitor.
December 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27785053/new-developments-in-the-management-of-non-small-cell-lung-cancer-focus-on-rociletinib-what-went-wrong
#16
REVIEW
Nele Van Der Steen, Chiara Caparello, Christian Rolfo, Patrick Pauwels, Godefridus J Peters, Elisa Giovannetti
Recently, the development of the third-generation epidermal growth factor receptor-small molecule inhibitor (EGFR-TKI) rociletinib had failed. In this review, the wide-ranging aspects of the evolution of EGFR-TKIs were collected, with a special focus on rociletinib. The influence of different oncogenic mutations on EGFR activity was also discussed. Resistance to the first (erlotinib, gefitinib)- and second (afatinib)-generation EGFR-TKIs provided the rationale behind the development of the third-generation inhibitors (rociletinib, osimertinib)...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27784815/osimertinib-in-the-treatment-of-patients-with-epidermal-growth-factor-receptor-t790m-mutation-positive-metastatic-non-small-cell-lung-cancer-clinical-trial-evidence-and-experience
#17
REVIEW
Ivana Sullivan, David Planchard
Patients with advanced epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) are particularly sensitive to treatment with first- or second-generation EGFR tyrosine kinase inhibitors such as gefitinib, erlotinib and afatinib, which block the cell-signaling pathways that drive the growth of tumor cells. Unfortunately, the majority of patients develop resistance to them after a median duration of response of around 10 months, and in over half of these patients the emergence of the EGFR T790M resistance mutation is detected...
December 2016: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/27770386/mechanisms-of-resistance-to-third-generation-egfr-tyrosine-kinase-inhibitors
#18
Shuhang Wang, Yongping Song, Feifei Yan, Delong Liu
The tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are becoming the first line of therapy for advanced non-small cell lung cancer (NSCLC). Acquired mutations in EGFR account for one of the major mechanisms of resistance to the TKIs. Three generations of EGFR TKIs have been used in clinical applications. AZD9291 (osimertinib; Tagrisso) is the first and only FDA approved third-generation EGFR TKI for T790M-positive advanced NSCLC patients. However, resistance to AZD9291 arises after 9-13 months of therapy...
October 21, 2016: Frontiers of Medicine
https://www.readbyqxmd.com/read/27751847/osimertinib-for-pretreated-egfr-thr790met-positive-advanced-non-small-cell-lung-cancer-aura2-a-multicentre-open-label-single-arm-phase-2-study
#19
Glenwood Goss, Chun-Ming Tsai, Frances A Shepherd, Lyudmila Bazhenova, Jong Seok Lee, Gee-Chen Chang, Lucio Crino, Miyako Satouchi, Quincy Chu, Toyoaki Hida, Ji-Youn Han, Oscar Juan, Frank Dunphy, Makoto Nishio, Jin-Hyoung Kang, Margarita Majem, Helen Mann, Mireille Cantarini, Serban Ghiorghiu, Tetsuya Mitsudomi
BACKGROUND: Osimertinib (AZD9291) is an oral, potent, irreversible EGFR tyrosine-kinase inhibitor selective for EGFR tyrosine-kinase inhibitor sensitising mutations, and the EGFR Thr790Met resistance mutation. We assessed the efficacy and safety of osimertinib in patients with EGFR Thr790Met-positive non-small-cell lung cancer (NSCLC), who had progressed after previous therapy with an approved EGFR tyrosine-kinase inhibitor. METHODS: In this phase 2, open-label, single-arm study (AURA2), patients aged at least 18 years with centrally confirmed EGFR Thr790Met-positive mutations, locally advanced or metastatic (stage IIIB/IV) NSCLC who progressed on previous EGFR tyrosine-kinase inhibitor therapy received osimertinib 80 mg orally once daily; treatment could continue beyond progression if the investigator observed a clinical benefit...
October 14, 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27751845/osimertinib-in-egfr-mutant-nsclc-how-to-select-patients-and-when-to-treat
#20
Jon Zugazagoitia, Irene Ferrer, Luis Paz-Ares
No abstract text is available yet for this article.
October 14, 2016: Lancet Oncology
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