keyword
MENU ▼
Read by QxMD icon Read
search

osimertinib

keyword
https://www.readbyqxmd.com/read/28420725/monitoring-daily-dynamics-of-early-tumor-response-to-targeted-therapy-by-detecting-circulating-tumor-dna-in-urine
#1
Hatim Husain, Vladislava O Melnikova, Karena Kosco, Brian Woodward, Soham More, Sandeep C Pingle, Elizabeth Weihe, Ben Ho Park, Muneesh Tewari, Mark G Erlander, Ezra E W Cohen, Scott M Lippman, Razelle Kurzrock
Purpose: Non-invasive drug biomarkers for the early assessment of tumor response can enable adaptive therapeutic decision-making and proof-of-concept studies for investigational drugs. Circulating tumor DNA (ctDNA) is released into the circulation by tumor cell turnover and has been shown to be detectable in urine. Experimental Design : We tested the hypothesis that dynamic changes in epidermal growth factor receptor (EGFR) activating (exon 19del and L858R) and resistance (T790M) mutation levels detected in urine could inform tumor response within days of therapy for advanced non-small cell lung cancer (NSCLC) patients receiving osimertinib, a second line third generation anti-EGFR tyrosine kinase inhibitor...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28419328/efficacy-and-safety-of-osimertinib-in-a-japanese-compassionate-use-program
#2
Yutaka Fujiwara, Yasushi Goto, Shintaro Kanda, Hidehito Horinouchi, Noboru Yamamoto, Naomi Sakiyama, Reiko Ando Makihara, Yuichiro Ohe
Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets the T790M mutation of EGFR. In 2016, AstraZeneca conducted a compassionate use program for osimertinib in Japan. Methods: Eighteen consecutive patients with histologically proven non-small-cell lung cancer (NSCLC) and harboring the T790M EGFR mutation participated in the compassionate use program between 1 April and 25 May 2016, at the National Cancer Center Hospital...
April 13, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28416737/efficacy-of-continuous-egfr-inhibition-and-role-of-hedgehog-in-egfr-acquired-resistance-in-human-lung-cancer-cells-with-activating-mutation-of-egfr
#3
Carminia Maria Della Corte, Umberto Malapelle, Elena Vigliar, Francesco Pepe, Giancarlo Troncone, Vincenza Ciaramella, Teresa Troiani, Erika Martinelli, Valentina Belli, Fortunato Ciardiello, Floriana Morgillo
PURPOSE: The aim of this work was to investigate the efficacy of sequential treatment with first-, second- and third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and the mechanisms of acquired resistance occurring during the sequential use of these inhibitors. EXPERIMENTAL DESIGN: We developed an in vivo model of acquired resistance to EGFR-inhibitors by treating nude mice xenografted with HCC827, a human non-small-cell lung cancer (NSCLC) cell line harboring EGFR activating mutation, with a sequence of first-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) (erlotinib and gefitinib), of second-generation EGFR-TKI (afatinib) plus/minus the anti-EGFR monoclonal antibody cetuximab, and of third-generation EGFR-TKI (osimertinib)...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416483/sfk-fak-signaling-attenuates-osimertinib-efficacy-in-both-drug-sensitive-and-drug-resistant-models-of-egfr-mutant-lung-cancer
#4
Eiki Ichihara, David Westover, Catherine B Meador, Yingjun Yan, Joshua A Bauer, Pengcheng Lu, Fei Ye, Amanda Kulick, Elisa De Stanchina, Robert McEwen, Marc Ladanyi, Darren Cross, William Pao, Christine M Lovly
Mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as osimertinib, are active agents for the treatment of EGFR-mutant lung cancer. Specifically, these agents can overcome the effects of the T790M mutation, which mediates resistance to first and second-generation EGFR TKI, and recent clinical trials have documented their efficacy in patients with EGFR-mutant lung cancer. Despite promising results, therapeutic efficacy is limited by development of acquired resistance...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28413660/dramatic-intracranial-response-to-osimertinib-in-a-poor-performance-status-patient-with-lung-adenocarcinoma-harboring-the-epidermal-growth-factor-receptor-t790m-mutation-a-case-report
#5
Takehiro Uemura, Tetsuya Oguri, Minami Okayama, Hiromi Furuta, Yoshihiro Kanemitsu, Osamu Takakuwa, Hirotsugu Ohkubo, Masaya Takemura, Ken Maeno, Yutaka Ito, Akio Niimi
We herein report a case of dramatic intracranial response to osimertinib in a poor performance status patient with lung adenocarcinoma harboring the epidermal growth factor receptor (EGFR) T790M mutation encoded in exon 20. The patient was a 59-year-old woman with EGFR exon 19 deletion-positive lung adenocarcinoma, who relapsed with multiple brain metastases. Computed tomography-guided biopsy of the left pleural tumor revealed adenocarcinoma harboring an EGFR exon 19 deletion and an EGFR T790M mutation encoded in exon 20...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28408617/treatment-paradigms-for-advanced-non-small-cell-lung-cancer-at-academic-medical-centers-involvement-in-clinical-trial-endpoint-design
#6
Charu Aggarwal, Hossein Borghaei
Based on the positive results of various clinical trials, treatment options for non-small cell lung cancer (NSCLC) have expanded greatly over the last 25 years. While regulatory approvals of chemotherapeutic agents for NSCLC have largely been based on improvements in overall survival, recent approvals of many targeted agents for NSCLC (afatinib, crizotinib, ceritinib, osimertinib) have been based on surrogate endpoints such as progression-free survival and objective response. As such, selection of appropriate clinical endpoints for examining the efficacy of investigational agents for NSCLC is of vital importance in clinical trial design...
April 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28404761/non-small-cell-lung-cancer-version-5-2017-nccn-clinical-practice-guidelines-in-oncology
#7
David S Ettinger, Douglas E Wood, Dara L Aisner, Wallace Akerley, Jessica Bauman, Lucian R Chirieac, Thomas A D'Amico, Malcolm M DeCamp, Thomas J Dilling, Michael Dobelbower, Robert C Doebele, Ramaswamy Govindan, Matthew A Gubens, Mark Hennon, Leora Horn, Ritsuko Komaki, Rudy P Lackner, Michael Lanuti, Ticiana A Leal, Leah J Leisch, Rogerio Lilenbaum, Jules Lin, Billy W Loo, Renato Martins, Gregory A Otterson, Karen Reckamp, Gregory J Riely, Steven E Schild, Theresa A Shapiro, James Stevenson, Scott J Swanson, Kurt Tauer, Stephen C Yang, Kristina Gregory, Miranda Hughes
This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.
April 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28367058/epidermal-growth-factor-receptor-t790m-mutation-positive-metastatic-non-small-cell-lung-cancer-focus-on-osimertinib-azd9291
#8
REVIEW
Nibal Saad, Aarati Poudel, Alina Basnet, Ajeet Gajra
Adenocarcinoma is the most common type of non-small-cell lung cancer (NSCLC). Adenocarcinoma with epidermal growth factor receptor (EGFR) mutations accounts for 8%-30% of all cases of NSCLC depending on the geography and ethnicity. EGFR-mutated NSCLC usually responds to first-line therapy with EGFR tyrosine kinase inhibitors (TKIs). However, there is eventual loss of efficacy to TKIs due to development of resistance. The most frequent cause for resistance is a second EGFR mutation in exon 20 (T790M), which is encountered in up to 62% of patients...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28359250/insight-into-discovery-of-next-generation-reversible-tmlr-inhibitors-targeting-egfr-activating-and-drug-resistant-t790m-mutants
#9
Subhash Mohan Agarwal, Divyani Pal, Mansi Gupta, Ravi Saini
Cancer is one of the most challenging diseases among the various causes of deaths worldwide. Among cancer, lung cancer rules as the leading cause of cancer-related deaths annually.The majority of the lung cancers identified are non-small cell lung cancer (NSCLC). Clinically, the Epidermal Growth Factor Receptor (EGFR) is a therapeutically accepted target for NSCLC. Many therapeutic leads that target this transmembrane receptor protein were tested for anti-EGFR activity that led to the discovery of gefitinib and erlotinib...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28353220/patient-experience-of-symptoms-and-side-effects-when-treated-with-osimertinib-for-advanced-non-small-cell-lung-cancer-a-qualitative-interview-substudy
#10
Anna Rydén, Fiona Blackhall, Hye Ryun Kim, Rathi N Pillai, Lauren Braam, Mona L Martin, Andrew Walding
INTRODUCTION: Capturing the patient experience during treatment is important to both regulatory authorities and to patients starting treatment. We identified the symptoms and side effects experienced by patients with advanced non-small-cell lung cancer during osimertinib treatment, to understand treatment expectations, satisfaction, and the level of difficulty coping with the side effects experienced during treatment. METHODS: Qualitative interviews (approximately 4-6 weeks after treatment initiation and again after approximately 4 months of treatment) were conducted during the phase I/II AURA clinical trial of osimertinib, a tyrosine kinase inhibitor of epidermal growth factor receptor-sensitizing and T790M resistance mutations...
March 28, 2017: Patient
https://www.readbyqxmd.com/read/28344665/treatment-choice-in-epidermal-growth-factor-receptor-mutation-positive-non-small-cell-lung-carcinoma-latest-evidence-and-clinical-implications
#11
REVIEW
Oscar Juan, Sanjay Popat
Discovery of sensitizing mutations in epidermal growth factor receptor (EGFR) and the subsequent development of EGFR tyrosine kinase inhibitors (TKIs) have substantially changed the treatment of lung cancer. First-line treatment with EGFR TKIs (gefitinib, erlotinib and afatinib) has demonstrated a superior response rate and progression-free survival (PFS) compared with chemotherapy in EGFR-mutation positive patients. However, a number of open questions remain, such as choice between the three EGFR TKIs licensed, treatment of patients unsuitable for chemotherapy due to morbidity or advanced age, management of acquired resistance and optimal biological sample to determine EGFR status...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28341106/the-apple-trial-feasibility-and-activity-of-azd9291-osimertinib-treatment-on-positive-plasma-t790m-in-egfr-mutant-nsclc-patients-eortc-1613
#12
Jordi Remon, Jessica Menis, Baktiar Hasan, Aleksandra Peric, Eleonora De Maio, Silvia Novello, Martin Reck, Thierry Berghmans, Bartosz Wasag, Benjamin Besse, Rafal Dziadziuszko
The AZD9291 (Osimertinib) Treatment on Positive PLasma T790M in EGFR-mutant NSCLC Patients (APPLE) trial is a randomized, open-label, multicenter, 3-arm, phase II study in advanced, epidermal growth factor receptor (EGFR)-mutant and EGFR tyrosine kinase inhibitor (TKI)-naive non-small-cell lung cancer (NSCLC) patients, to evaluate the best strategy for sequencing gefitinib and osimertinib treatment. Advanced EGFR-mutant NSCLC patients, with World Health Organization performance status 0-2 who are EGFR TKI treatment-naive and eligible to receive first-line treatment with EGFR TKI will be randomized to: In all arms, a plasmatic ctDNA T790M test will be performed by a central laboratory at the Medical University of Gdansk (Poland) but will be applied as a predictive marker for making treatment decisions only in arm B...
March 1, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28332047/mechanisms-of-resistance-to-target-therapies-in-non-small-cell-lung-cancer
#13
Francesco Facchinetti, Claudia Proto, Roberta Minari, Marina Garassino, Marcello Tiseo
Targeted therapies are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements, has changed the treatment landscape while improving the prognosis of lung cancer patients. Inevitably, virtually all patients initially treated with targeted therapies develop resistance because of the emergence of an insensitive cellular population, selected by pharmacologic pressure. Diverse mechanisms of resistance, in particular to EGFR, ALK and ROS1 tyrosine-kinase inhibitors (TKIs), have now been discovered and may be classified in three different groups: (1) alterations in the target (such as EGFR T790M and ALK or ROS1 mutations); (2) activation of alternative pathways (i...
March 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28302223/-current-status-and-prospect-of-t790m-mutation-in-non-small-cell-lung-cancer
#14
REVIEW
Qin Yu, Da Jiang, Ying Li
Targeted therapy with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) is regarded as the main accepted first-line treatment on EGFR mutation in non-small cell lung cancer (NSCLC). Although targeted therapy for the first and two generation of TKIs may lead to longer progression-free survival (PFS) and better tolerance for patients, the long-term treatment will inevitably lead to drug resistance. Among them, more than 50% of acquired resistance is associated with T790M mutation. The latest guidelines from the National Comprehensive Cancer Network (NCCN) have been proposed that the three generation of TKI (Osimertinib) can be used in first-line TKI therapy progress with detecting T790M mutations in patients...
March 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28296233/sustained-response-to-standard-dose-osimertinib-in-a-patient-with-plasma-t790m-positive-leptomeningeal-metastases-from-primary-lung-adenocarcinoma
#15
Oscar Siu-Hong Chan, Warren Kam-Wing Leung, Rebecca Mei-Wan Yeung
A 44-year-old male, never smoker, suffers from stage IV adenocarcinoma of the right lung with epidermal growth factor receptor (EGFR) exon-21 L858R point mutation on initial presentation. After 23 months of treatment with gefitinib, intercalated with multiple courses of radiotherapy, leptomeningeal metastases (LMs) developed. Acquired T790M mutation was confirmed by the droplet digital polymerase chain reaction plasma EGFR test. After switching to osimertinib at the standard dose, his neurocognitive function improved clinically, coupled with sustained radiological improvement...
March 15, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28293555/second-line-treatment-of-non-small-cell-lung-cancer-clinical-pathological-and-molecular-aspects-of-nintedanib
#16
REVIEW
Luis Corrales, Amanda Nogueira, Francesco Passiglia, Angela Listi, Christian Caglevic, Marco Giallombardo, Luis Raez, Edgardo Santos, Christian Rolfo
Lung carcinoma is the leading cause of death by cancer in the world. Nowadays, most patients will experience disease progression during or after first-line chemotherapy demonstrating the need for new, effective second-line treatments. The only approved second-line therapies for patients without targetable oncogenic drivers are docetaxel, gemcitabine, pemetrexed, and erlotinib and for patients with target-specific oncogenes afatinib, osimertinib, crizotinib, alectinib, and ceritinib. In recent years, evidence on the role of antiangiogenic agents have been established as important and effective therapeutic targets in non-small cell lung cancer (NSCLC)...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28287083/brigatinib-combined-with-anti-egfr-antibody-overcomes-osimertinib-resistance-in-egfr-mutated-non-small-cell-lung-cancer
#17
Ken Uchibori, Naohiko Inase, Mitsugu Araki, Mayumi Kamada, Shigeo Sato, Yasushi Okuno, Naoya Fujita, Ryohei Katayama
Osimertinib has been demonstrated to overcome the epidermal growth factor receptor (EGFR)-T790M, the most relevant acquired resistance to first-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, the C797S mutation, which impairs the covalent binding between the cysteine residue at position 797 of EGFR and osimertinib, induces resistance to osimertinib. Currently, there are no effective therapeutic strategies to overcome the C797S/T790M/activating-mutation (triple-mutation)-mediated EGFR-TKI resistance...
March 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28284589/osimertinib-improves-progression-free-survival-in-nsclc
#18
Sheila Pinion
No abstract text is available yet for this article.
March 8, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28274957/an-acquired-her2-t798i-gatekeeper-mutation-induces-resistance-to-neratinib-in-a-patient-with-her2-mutant-driven-breast-cancer
#19
Ariella B Hanker, Monica Red Brewer, Jonathan H Sheehan, James P Koch, Gregory R Sliwoski, Rebecca Nagy, Richard Lanman, Michael F Berger, David M Hyman, David B Solit, Jie He, Vincent Miller, Richard E Cutler, Alshad S Lalani, Darren Cross, Christine M Lovly, Jens Meiler, Carlos L Arteaga
We report a HER2T798I gatekeeper mutation in a patient with HER2L869R-mutant breast cancer with acquired resistance to neratinib. Laboratory studies suggested that HER2L869R is a neratinib-sensitive, gain-of-function mutation that upon dimerization with mutant HER3E928G, also present in the breast cancer, amplifies HER2 signaling. The patient was treated with neratinib and exhibited a sustained partial response. Upon clinical progression, HER2T798I was detected in plasma tumor cell-free DNA. Structural modeling of this acquired mutation suggested that the increased bulk of isoleucine in HER2T798I reduces neratinib binding...
March 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28274743/tolerable-and-effective-combination-of-full-dose-crizotinib-and-osimertinib-targeting-met-amplification-sequentially-emerging-after-t790m-positivity-in-egfr-mutant-non-small-cell-lung-cancer
#20
Emily R York, Marileila Varella-Garcia, Tami J Bang, Dara L Aisner, D Ross Camidge
No abstract text is available yet for this article.
March 6, 2017: Journal of Thoracic Oncology
keyword
keyword
95854
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"