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Egfr-tki treatment for lung cancer

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https://www.readbyqxmd.com/read/29328407/estrogen-receptor-%C3%AE-1-activation-accelerates-resistance-to-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer
#1
Shengling Fu, Changyu Liu, Quanfu Huang, Sheng Fan, Hexiao Tang, Xiangning Fu, Bo Ai, Yongde Liao, Qian Chu
Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR‑TKIs) have revolutionized the treatment of patients with advanced EGFR-mutant NSCLC. However, drug resistance eventually develops in the majority of patients despite an excellent initial response. The present study aimed to investigate the mechanism of acquired resistance to EGFR-TKIs and to explore strategies to overcome the resistance to EGFR-TKIs from a gender perspective...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29327061/egfr-tki-associated-interstitial-pneumonitis-in-nivolumab-treated-patients-with-non-small-cell-lung-cancer
#2
Yasuo Oshima, Tetsuya Tanimoto, Koichiro Yuji, Arinobu Tojo
Importance: Nivolumab and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are now the standard-of-care therapies in non-small cell lung cancer (NSCLC). Although EGFR-TKIs are well understood and have well-defined safety profiles, our experience with immune checkpoint inhibitors is still growing, particularly regarding the use of combinations of different classes of antitumor agents, including both the concomitant and sequential use of such agents. Objective: To determine whether nivolumab increases EGFR-TKI-associated interstitial pneumonitis (IP)...
January 11, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29325035/amplicon-based-next-generation-sequencing-of-plasma-cell-free-dna-for-detection-of-driver-and-resistance-mutations-in-advanced-non-small-cell-lung-cancer
#3
N Guibert, Y Hu, N Feeney, Y Kuang, V Plagnol, G Jones, K Howarth, J F Beeler, C P Paweletz, G R Oxnard
Background: Genomic analysis of plasma cell-free DNA is transforming lung cancer care, however available assays are limited by cost, turnaround time, and imperfect accuracy. Here we study amplicon-based plasma next-generation sequencing (NGS), rather than hybrid-capture-based plasma NGS, hypothesizing this would allow sensitive detection and monitoring of driver and resistance mutations in advanced non-small cell lung cancer (NSCLC). Methods: Plasma samples from patients with NSCLC and a known targetable genotype (EGFR, ALK/ROS1 and other rare genotypes) were collected while on therapy and analyzed, blinded to tumor genotype...
January 9, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29317191/randomized-double-blind-phase-ib-iii-study-of-erlotinib-with-ramucirumab-or-placebo-in-previously-untreated-egfr-mutant-metastatic-non-small-cell-lung-cancer-relay-phase-ib-results
#4
Martin Reck, Edward B Garon, Luis Paz-Ares, Santiago Ponce, Jesus Corral Jaime, Oscar Juan, Ernest Nadal, Katsuyuki Kiura, Ryan C Widau, Shuang He, Rita Dalal, Pablo Lee, Kazuhiko Nakagawa
BACKGROUND: Despite the likelihood of an initial response to an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), EGFR-mutant non-small-cell lung cancer (NSCLC) patients develop disease progression. Antiangiogenic agents in combination with an EGFR TKI might provide additional benefit in patients with EGFR-mutant NSCLC. In this article we report safety, exposure, and progression-free survival (PFS) results for part A (phase Ib) of RELAY, a randomized, double-blind, phase Ib/III study investigating safety and efficacy of erlotinib (EGFR TKI) with ramucirumab (anti-vascular endothelial growth factor receptor-2 antibody) or placebo in first-line EGFR-mutant stage IV NSCLC...
November 21, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29312741/disease-free-survival-improved-by-use-of-adjuvant-egfr-tyrosine-kinase-inhibitors-in-resectable-non-small-cell-lung-cancer-an-updated-meta-analysis
#5
Yonggang Yuan, Qingyuan Huang, Chang Gu, Haiquan Chen
Background: A previous meta-analysis of our research team suggested survival advantage from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) after surgery in patients with EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to follow up on the findings of the previous one and presents our latest updates through the past few years. Methods: The study advanced the previous meta-analysis and included a comprehensive range of relevant studies in PubMed...
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29299405/clinical-management-of-epidermal-growth-factor-receptor-mutation-positive-non-small-cell-lung-cancer-patients-after-progression-on-previous-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-the-necessity-of-repeated-molecular-analysis
#6
REVIEW
José Luís González-Larriba, Martín Lázaro-Quintela, Manuel Cobo, Manuel Dómine, Margarita Majem, Rosario García-Campelo
One of the most important advances in the treatment of non-small cell lung cancer (NSCLC) has been the identification of molecular alterations vulnerable to targeted inhibition, such as mutations in the epidermal growth factor receptor (EGFR) gene. EGFR tyrosine kinase inhibitors (EGFR-TKIs) are targeted agents used to treat EGFR mutation-positive advanced NSCLC showing significant improvements in terms of response rate (RR) and progression-free survival (PFS) compared to conventional chemotherapy. However, all patients eventually develop resistance to first-line EGFR-TKIs...
December 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29298799/targeting-her2-aberrations-in-non-small-cell-lung-cancer-with-osimertinib
#7
Shengwu Liu, Shuai Li, Josephine Hai, Xiaoen Wang, Ting Chen, Max M Quinn, Peng Gao, Yanxi Zhang, Hongbin Ji, Darren Cross, Kwok-Kin Wong
PURPOSE: HER2 (or ERBB2) aberrations, including both amplification and mutations, have been classified as oncogenic drivers that contribute to 2-6 percent of lung adenocarcinomas. HER2 amplification is also an important mechanism for acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). However, due to limited preclinical studies and clinical trials, currently there is still no available standard of care for lung cancer patients with HER2 aberrations. To fulfill the clinical need for targeting HER2 in non-small cell lung cancer (NSCLC) patients, we performed a comprehensive pre-clinical study to evaluate the efficacy of a third-generation TKI, osimertinib (AZD9291)...
January 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29290998/detection-of-somatic-variants-and-egfr-mutations-in-cell-free-dna-from-non-small-cell-lung-cancer-patients-by-ultra-deep-sequencing-using-the-ion-ampliseq-cancer-hotspot-panel-and-droplet-digital-polymerase-chain-reaction
#8
Jae Sook Sung, Hyon Yong Chong, Nak-Jung Kwon, Hae Mi Kim, Jong Won Lee, Boyeon Kim, Saet Byeol Lee, Chang Won Park, Jung Yoon Choi, Won Jin Chang, Yoon Ji Choi, Sung Yong Lee, Eun Joo Kang, Kyong Hwa Park, Yeul Hong Kim
Highly sensitive genotyping assays can detect mutations in cell-free DNA (cfDNA) from cancer patients, reflecting the biology of each patient's cancer. Because circulating tumor DNA comprises a small, variable fraction of DNA circulating in the blood, sensitive parallel multiplexing tests are required to determine mutation profiles. We prospectively examined the clinical utility of ultra-deep sequencing analysis of cfDNA from 126 non-small cell lung cancer (NSCLC) patients using the Ion AmpliSeq Cancer Hotspot Panel v2 (ICP) and validated these findings with droplet digital polymerase chain reaction (ddPCR)...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290257/primary-resistance-to-osimertinib-due-to-sclc-transformation-issue-of-t790m-determination-on-liquid-re-biopsy
#9
R Minari, P Bordi, M Del Re, F Facchinetti, F Mazzoni, F Barbieri, A Camerini, C E Comin, L Gnetti, C Azzoni, R Nizzoli, B Bortesi, E Rofi, P Petreni, N Campanini, G Rossi, R Danesi, M Tiseo
OBJECTIVES: EGFR T790M mutation is the most common mechanism of resistance to first-/second-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) and could be overcome by third-generation EGFR-TKIs, such as osimertinib. Liquid biopsy, a non-invasive technique used to test the presence of the resistant mutation, may help avoiding tissue re-biopsy. However, analysing only circulating-free DNA, information about other less frequent and coexisting resistance mechanisms may remain unrevealed...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29290249/a-phase-i-trial-of-afatinib-and-bevacizumab-in-chemo-na%C3%A3-ve-patients-with-advanced-non-small-cell-lung-cancer-harboring-egfr-mutations-okayama-lung-cancer-study-group-trial-1404
#10
Takashi Ninomiya, Naoyuki Nogami, Toshiyuki Kozuki, Daijiro Harada, Toshio Kubo, Kadoaki Ohashi, Shoichi Kuyama, Kenichiro Kudo, Akihiro Bessho, Nobuaki Fukamatsu, Nobukazu Fujimoto, Keisuke Aoe, Takuo Shibayama, Keisuke Sugimoto, Nagio Takigawa, Katsuyuki Hotta, Katsuyuki Kiura
OBJECTIVE: In advanced epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC), treatment with afatinib, a second-generation EGFR-tyrosine kinase inhibitor (TKI), confers a significant survival benefit over platinum-based chemotherapy. The first-generation EGFR-TKIs gefitinib and erlotinib in combination with bevacizumab have improved progression-free survival. We hypothesized that the combination of afatinib with bevacizumab would further improve efficacy, and conducted a phase I trial to test this hypothesis...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29285395/paradoxical-response-to-osimertinib-therapy-in-a-patient-with-t790m-mutated-lung-adenocarcinoma
#11
Shinichiro Okauchi, Hajime Osawa, Kunihiko Miyazaki, Mio Kawaguchi, Hiroaki Satoh
A 'paradoxical response' to cancer treatment is a term used to describe the emergence of unexpected new lesions and the progression of existing lesions, despite appropriate and effective therapy. 'Pseudo-progression' is a phenomenon in which lymphocytes activated by an immune checkpoint inhibitor accumulate in a tumor and expand its shadow, mimicking enlargement of the primary lesion or development of a new metastatic lesion. Patients receiving cancer chemotherapy may respond differently to treatment, by exhibiting a response, deterioration, or the simultaneous occurrence of both...
January 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29285266/characterization-of-the-efficacies-of-osimertinib-and-nazartinib-against-cells-expressing-clinically-relevant-epidermal-growth-factor-receptor-mutations
#12
Keita Masuzawa, Hiroyuki Yasuda, Junko Hamamoto, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Kenzo Soejima, Tomoko Betsuyaku
Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) were developed to overcome EGFR T790M-mediated resistance to first- and second-generation EGFR-TKIs. Third-generation EGFR-TKIs, such as osimertinib and nazartinib, are effective for patients with the EGFR T790M mutation. However, there are no direct comparison data to guide the selection of a third-generation EGFR-TKI for patients with different EGFR mutations. We previously established an in vitro model to estimate the therapeutic windows of EGFR-TKIs by comparing their relative efficacies against cells expressing mutant or wild type EGFRs...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29277186/-current-status-and-progress-in-molecular-imaging-of-non-small-cell-lung-%C3%A2-cancer-for-molecular-targeted-egfr-tki-treatment-sensitivity-and-%C3%A2-treatment-tolerance-prediction
#13
Dong Dai, Wengui Xu, Qi Wang, Xiaofeng Li, Yanjia Zhu
More than 80% of lung cancer is non-small cell lung cancer (NSCLC), and the epidermal growth factor receptor (EGFR)-mediated signaling pathway is closely related to the occurrence and development of NSCLC. Small molecule EGFR-tyrosine kinase inhibitors (EGFR-TKI) targeting EGFR have been used in the clinical treatment of NSCLC, and positron emission tomography/computed tomgraphy (PET/CT) imaging can noninvasively monitor the expression and mutation status of EGFR in patients with NSCLC. 18F-FDG PET/CT imaging has predictive value for the activation of EGFR mutation and EGFR-TKI treatment efficacy, and in vivo can be directly observed drugs and systemic tumor targeting EGFR combined with the specific circumstances, by PET/CT imaging before and after treatment, to achieve dynamic monitoring, guide the therapy before treatment and treatment of sensitive population screening process, to achieve NSCLC EGFR-TKI precise treatment is essential...
December 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29249325/outcomes-in-patients-with-non-small-cell-lung-cancer-and-acquired-thr790met-mutation-treated-with-osimertinib-a-genomic-study
#14
Chia-Chi Lin, Jin-Yuan Shih, Chong-Jen Yu, Chao-Chi Ho, Wei-Yu Liao, Jih-Hsing Lee, Tzu-Hsiu Tsai, Kang-Yi Su, Min-Shu Hsieh, Yih-Leong Chang, Ya-Ying Bai, Derek De-Rui Huang, Kenneth S Thress, James Chih-Hsin Yang
BACKGROUND: Osimertinib is approved for the treatment of non-small-cell lung cancer in patients who develop the EGFR Thr790Met mutation after treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). We assessed outcomes in patients with non-small-cell lung cancer and the EGFR Thr790Met mutation who were treated with osimertinib, a third-generation EGFR TKI, after previous treatment failure with one or more other EGFR TKIs. METHODS: Eligible patients had been enrolled at one centre in the AURA study, had shown resistance to a previous EGFR TKI, and had EGFR-activating mutations and acquired Thr790Met mutation detectable in tumour tissue or plasma...
December 14, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29247383/adjusted-indirect-comparison-using-propensity-score-matching-of-osimertinib-to-platinum-based-doublet-chemotherapy-in-patients-with-egfrm-t790m-nsclc-who-have-progressed-after-egfr-tki
#15
Helen Mann, Frank Andersohn, Carolyn Bodnar, Tetsuya Mitsudomi, Tony S K Mok, James Chih-Hsin Yang, Christopher Hoyle
BACKGROUND AND OBJECTIVE: An adjusted indirect comparison was conducted to assess efficacy outcomes, particularly overall survival (OS), of osimertinib versus platinum-based doublet chemotherapy in patients with epidermal growth factor receptor-mutated (EGFRm) T790M mutation-positive non-small-cell lung cancer (NSCLC) who had progressed following an EGFR tyrosine kinase inhibitor (TKI). Analysis of treatment effect from two separate trials had the potential to more accurately estimate the magnitude of OS benefit due to absence of confounding due to treatment switching from the control arm to the osimertinib arm of the ongoing randomized control trial, AURA3...
December 15, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29242281/fda-benefit-risk-assessment-of-osimertinib-for-the-treatment-of-metastatic-non-small-cell-lung-cancer-harboring-epidermal-growth-factor-receptor-t790m-mutation
#16
Lauretta Odogwu, Luckson Mathieu, Kirsten B Goldberg, Gideon M Blumenthal, Erin Larkins, Mallorie H Fiero, Lisa Rodriguez, Karen Bijwaard, Eunice Y Lee, Reena Philip, Ingrid Fan, Martha Donoghue, Patricia Keegan, Amy McKee, Richard Pazdur
On March 30, 2017, the U.S. Food and Drug Administration (FDA) approved osimertinib for the treatment of patients with metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive, non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed following EGFR tyrosine kinase inhibitor (TKI) therapy. Approval was based on demonstration of a statistically significant difference in the primary endpoint of progression-free survival (PFS) when comparing osimertinib with chemotherapy in an international, multicenter, open-label, randomized trial (AURA3)...
December 14, 2017: Oncologist
https://www.readbyqxmd.com/read/29239002/pharmacokinetics-of-osimertinib-in-chinese-patients-with-advanced-nsclc-a-phase-1-study
#17
Hongyun Zhao, Junning Cao, Jianhua Chang, Zhenxian Zhang, Li Yang, Jia Wang, Mireille Cantarini, Li Zhang
Osimertinib is an oral, irreversible, central nervous system active epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) selective for both EGFR-TKI sensitizing and T790M resistance mutations. The study's (NCT02529995) primary objective was to characterize the pharmacokinetics (PK) of osimertinib and its metabolites in Chinese patients enrolled in China. PK was assessed following single and multiple doses of 40 or 80 mg osimertinib once daily. Patients were aged ≥ 18 years with locally advanced or metastatic EGFR-TKI-sensitizing (EGFRm) non-small cell lung cancer and World Health Organization performance status of 0/1, who had progressed following prior EGFR-TKI...
December 14, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29227909/navigating-the-no-man-s-land-of-tki-failed-egfr-mutated-non-small-cell-lung-cancer-nsclc-a-review
#18
REVIEW
Bryan Oronsky, Patrick Ma, Tony R Reid, Pedro Cabrales, Michelle Lybeck, Arnold Oronsky, Neil Oronsky, Corey A Carter
As the leading cause of cancer-related mortality, lung cancer is a worldwide health issue that is overwhelmingly caused by smoking. However, a substantial minority (~25%) of patients with non-small cell lung cancer (NSCLC) has never smoked. In these patients, activating mutations of the epidermal growth factor receptor (EGFR) are more likely, which render their tumors susceptible for a finite period to treatment with EGFR tyrosine kinase inhibitors (TKIs) and confer a better prognosis than EGFR wild-type NSCLC...
January 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29225480/role-of-afatinib-in-the-treatment-of-advanced-lung-squamous-cell-carcinoma
#19
REVIEW
Tiziana Vavalà
Lung cancer treatment has considerably changed over the last few years: the identification of druggable oncogenic alterations and innovative immunotherapic approaches granted lung cancer patients the possibility of more efficient and less toxic therapeutic options than chemotherapy. Nowadays, lung squamous cell carcinomas (SqCCs) patients have the chance to benefit from novel treatment alternatives, including immune checkpoint blockade and anti-angiogenic agents and, given positive trial results, from afatinib, a second generation tyrosine kinase inhibitor (TKI) that irreversibly antagonizes ErbB family tyrosine kinase receptors...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/29225262/the-effectiveness-of-afatinib-in-a-patient-with-advanced-lung-adenocarcinoma-harboring-rare-g719x-and-s768i-mutations
#20
Masahiro Watanabe, Satoshi Oizumi, Shizuka Kiuchi, Noriyuki Yamada, Hiroshi Yokouchi, Shinichi Fukumoto, Masao Harada
The uncommon mutations in the EGFR (the epithelial growth factor receptor) gene include a heterogeneous group of genomic alterations within exons 18-21. The clinical response of patients with such mutations to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment, however, remains unclear. We herein report a case of advanced lung adenocarcinoma harboring complex exon 18 G719X (Gly719Xaa) and exon 20 S768I (Ser768Ile) mutations. The patient started to receive afatinib and has exhibited good response without progression for 12 months...
December 8, 2017: Internal Medicine
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