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Egfr-tki treatment for lung cancer

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https://www.readbyqxmd.com/read/29123416/frequency-and-clinical-relevance-of-egfr-mutations-and-eml4-alk-translocations-in-octogenarians-with-non-small-cell-lung-cancer
#1
Amanda Tufman, Kathrin Kahnert, Thomas Duell, Diego Kauffmann-Guerrero, Katrin Milger, Christian Schneider, Julia Stump, Zulfiya Syunyaeva, Rudolf Maria Huber, Simone Reu
Background: Tyrosine kinase inhibitors (TKIs) have improved response rates in some patients with non-small cell lung cancer (NSCLC), and testing for EGFR mutation and ALK translocation is recommended for all patients with advanced lung adenocarcinoma. The frequency of driver mutations in elderly and very elderly patients has not been described. Patients and methods: We reviewed EGFR and ALK in patients over the age of 70 years diagnosed and treated at our center in 2015 (subgroups: 70-74, 75-79 and >80 years)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29121501/does-c-met-remain-a-rational-target-for-therapy-in-patients-with-egfr-tki-resistant-non-small-cell-lung-cancer
#2
REVIEW
Yi-Long Wu, Ross Andrew Soo, Giuseppe Locatelli, Uz Stammberger, Giorgio Scagliotti, Keunchil Park
Non-small cell lung cancer (NSCLC) inevitably develops resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. In 5-20% of cases, this can be attributed to aberrant c-Met activity, providing a clear rationale for the use of c-Met inhibitors in these patients. EGFR TKI-resistant tumors often remain sensitive to EGFR signaling, such that c-Met inhibitors are likely to be most effective when combined with continued EGFR TKI therapy. The phase III trials of the c-Met inhibitors onartuzumab and tivantinib, which failed to demonstrate significant benefit in patients with NSCLC but excluded patients with EGFR TKI-resistant disease, do not allow c-Met to be dismissed as a rational target in EGFR TKI-resistant NSCLC...
October 25, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29119113/increased-egfr-phosphorylation-correlates-with-higher-programmed-death-ligand-1-expression-analysis-of-tki-resistant-lung-cancer-cell-lines
#3
Kenichi Suda, Leslie Rozeboom, Koh Furugaki, Hui Yu, Mary Ann C Melnick, Kim Ellison, Christopher J Rivard, Katerina Politi, Tetsuya Mitsudomi, Fred R Hirsch
Despite the recent development of immunotherapies that target programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) treatment, these therapies are less effective in NSCLC patients with epidermal growth factor receptor (EGFR) mutations. However, the molecular mechanisms underlying this lower efficacy of immunotherapies in EGFR mutant lung cancers are still unclear. In this study, we analyzed PD-L1 protein expression in lung cancer cell lines with EGFR mutations prior to and after acquisition of resistance to EGFR tyrosine kinase inhibitors (TKIs)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29118262/stress-hormones-promote-egfr-inhibitor-resistance-in-nsclc-implications-for-combinations-with-%C3%AE-blockers
#4
Monique B Nilsson, Huiying Sun, Lixia Diao, Pan Tong, Diane Liu, Lerong Li, Youhong Fan, Alissa Poteete, Seung-Oe Lim, Kathryn Howells, Vincent Haddad, Daniel Gomez, Hai Tran, Guillermo Armaiz Pena, Lecia V Sequist, James C Yang, Jing Wang, Edward S Kim, Roy Herbst, J Jack Lee, Waun Ki Hong, Ignacio Wistuba, Mien-Chie Hung, Anil K Sood, John V Heymach
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance mediated by T790M-independent mechanisms remains a major challenge in the treatment of non-small cell lung cancer (NSCLC). We identified a targetable mechanism of EGFR inhibitor resistance whereby stress hormones activate β2-adrenergic receptors (β2-ARs) on NSCLC cells, which cooperatively signal with mutant EGFR, resulting in the inactivation of the tumor suppressor, liver kinase B1 (LKB1), and subsequently induce interleukin-6 (IL-6) expression...
November 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29111173/epidermal-growth-factor-receptor-mutation-predicts-favorable-outcomes-in-non-small-cell-lung-cancer-patients-with-brain-metastases-treated-with-stereotactic-radiosurgery
#5
Wen-Chi Yang, Furen Xiao, Jin-Yuan Shih, Chao-Chi Ho, Ya-Fang Chen, Ham-Min Tseng, Kuan-Yu Chen, Wei-Yu Liao, Chong-Jen Yu, James Chih-Hsin Yang, Sung-Hsin Kuo, Jason Chia-Hsien Cheng, Pan-Chyr Yang, Feng-Ming Hsu
PURPOSE: The impact of epidermal growth factor receptor (EGFR) mutations on radiotherapy for brain metastases (BM) is undetermined. We evaluated the effects of EGFR mutation status on responses and outcomes in non-small cell lung cancer (NSCLC) patients with BM, treated with upfront or salvage stereotactic radiosurgery (SRS). METHODS AND MATERIALS: From 2008 to 2015, 147 eligible NSCLC patients with 300 lesions were retrospectively analyzed. Patterns of tyrosine kinase inhibitor (TKI) therapy were recorded...
October 27, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29110841/heterogeneous-resistance-mechanisms-in-an-egfr-exon-19-mutated-non-small-cell-lung-cancer-patient-treated-with-erlotinib-persistent-fgfr3-mutation-localized-transformation-to-egfr-mutated-sclc-and-acquired-t790m-egfr-mutation
#6
Eric Santoni-Rugiu, Morten Grauslund, Linea C Melchior, Junia C Costa, Jens B Sørensen, Edyta M Urbanska
Patients with epidermal growth factor receptor (EGFR) gene-mutated non-small cell lung cancer (NSCLC) obtain substantial clinical benefit from EGFR tyrosine-kinase inhibitors (TKIs), but will ultimately develop TKI-resistance resulting in median progression-free survival of 9-15 months during first-line TKI-therapy. However, type and timing of TKI-resistance cannot be predicted and several mechanisms may simultaneously/subsequently occur during TKI-treatment. In this respect, we present a 49 year-old Caucasian male ex-smoker with metastatic pulmonary adenocarcinoma (ADC) that concomitantly harbored an EGFR exon 19-mutation (p...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29110836/next-generation-sequencing-reveals-novel-resistance-mechanisms-and-molecular-heterogeneity-in-egfr-mutant-non-small-cell-lung-cancer-with-acquired-resistance-to-egfr-tkis
#7
Choong-Kun Lee, Sora Kim, Jae Seok Lee, Jeong Eun Lee, Sung-Moo Kim, In Seok Yang, Hye Ryun Kim, Jeong Ho Lee, Sangwoo Kim, Byoung Chul Cho
OBJECTIVES: Despite initial responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutant non-small cell lung cancer, patients invariably develop acquired resistance. In this study, we performed next-generation sequencing in pre- and post-EGFR-TKI tumor samples to identify novel resistance mechanisms to EGFR-TKIs. MATERIAL AND METHODS: We collected tumor tissues before EGFR-TKI treatment and after progression from 19 NSCLC patients to analyze genomic alterations in 409 cancer related genes...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29108922/use-of-erlotinib-and-thalidomide-in-advanced-nsclc-patients-with-acquired-resistance-to-erlotinib-a-pilot-study
#8
Gen-He Wang, Peng-Fei Wu, Long-Hui Zhang, Ping Fang, Yong Chen, Gang Zuo, Yi-Qing Wu, Shu-Hong Wang, Guo-Ping Sun
Evidences suggested that combined blockade of the VEGF and EGFR pathways can improve the treatment efficacy of non-small-cell lung cancer (NSCLC). In our previously clinical practice, we observed that thalidomide, a potent VEGF inhibitor, can significantly decrease the tumor size of one EGFR-TKI resistance patient with lung cancer cachexia. In this pilot study, we tried to assess the efficacy and toxicity of the combination therapy of erlotinib and thalidomide in advanced NSCLC patients with acquired resistance to erlotinib...
October 18, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29104613/impact-of-exon-19-versus-exon-21-egfr-activating-mutation-on-outcomes-with-upfront-pemetrexed-carboplatin-chemotherapy
#9
Vanita Noronha, Vijay Patil, Amit Joshi, Anuradha Chougule, Atanu Bhattacharjee, Rajiv Kumar, Sucheta More, Supriya Goud, Ashay Karpe, Anant Ramaswamy, Nikhil Pande, Arun Chandrasekharan, Alok Goel, Vikas Talreja, Abhishek Mahajan, Amit Janu, Nilendu Purandare, Kumar Prabhash
Background: EGFR mutation subtype is a recognised factor impacting outcomes of patients receiving oral tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). Evidence for the effect of this factor on outcomes in patients receiving pemetrexed is limited. Methods: We completed a study comparing pemetrexed-platinum combination versus oral TKI in EGFR mutation-positive patients in lung cancer. We analysed the impact of EGFR mutation subtype, specifically, exon 19 and 21 on the PFS and OS of patients treated with pemetrexed (500 mg/m(2) on day 1) and carboplatin (AUC 5 on day 1) as first-line therapy...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/29101057/cost-effectiveness-of-osimertinib-for-egfr-mutation-positive-non-small-cell-lung-cancer-after-progression-of-first-line-egfr-tki-therapy
#10
Bin Wu, Xiaohua Gu, Qiang Zhang
INTRODUCTION: To investigate the cost-effectiveness of osimertinib for the treatment of advanced non-small-cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) T790M mutation after the failure of first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy. METHODS: A mathematical model was established by combining a decision tree and the Markov approach to project the cost-effectiveness of osimertinib for the treatment of patients who harbor an EGFR T790M mutation compared to that of standard chemotherapy, who had disease progression after first-line EGFR-TKI therapy with or without metastases to the central nervous system...
October 31, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29100434/oncogenic-driver-mutations-treatment-and-egfr-tki-resistance-in-a-caucasian-population-with-non-small-cell-lung-cancer-survival-in-clinical-practice
#11
Martin Faehling, Birgit Schwenk, Sebastian Kramberg, Robert Eckert, Anna-Lena Volckmar, Albrecht Stenzinger, Jörn Sträter
Introduction: Oncogenic driver mutations activating EGFR, ALK, or BRAF in NSCLC predict sensitivity to specific tyrosine-kinase inhibitors (TKIs). We provide data on prevalence, treatment and survival of driver-mutation positive NSCLC in a predominantly Caucasian population in routine clinical practice. Patients and Methods: NSCLC patients diagnosed from 2006-2015 with an EGFR-test result were included (n=265). Testing for EGFR, ALK, or BRAF was performed if specific TKI therapy was considered...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099567/duodenal-perforation-secondary-to-erlotinib-therapy-in-a-patient-with-non-small-cell-lung-cancer
#12
Rafiullah, Wardah Sayed Shah, Navid Abdul Majid, Rezwan Islam
Lung cancer is a lethal disease with high mortality, and treatment modality varies with type of tumor and stage of the disease. Targeted molecular therapies have been developed for patients with advanced non-small cell lung cancer. The presence of epidermal growth factor receptor (EGFR) mutation qualifies the patient for EGFR-TKI (tyrosine kinase inhibitor) therapy such as erlotinib, which is not without risk. We report an interesting case of duodenal perforation secondary to erlotinib therapy. This is the second reported case of bowel perforation after erlotinib therapy in a patient with advanced non-small cell lung cancer...
February 2017: WMJ: Official Publication of the State Medical Society of Wisconsin
https://www.readbyqxmd.com/read/29097733/discovery-of-targetable-genetic-alterations-in-advanced-non-small-cell-lung-cancer-using-a-next-generation-sequencing-based-circulating-tumor-dna-assay
#13
Helei Hou, Xiaonan Yang, Jinping Zhang, Zhe Zhang, Xiaomei Xu, Xiaoping Zhang, Chuantao Zhang, Dong Liu, Weihua Yan, Na Zhou, Hongmei Zhu, Zhaoyang Qian, Zhuokun Li, Xiaochun Zhang
Next-generation sequencing (NGS)-based circulating tumor DNA (ctDNA) assays have provided a new method of identifying tumor-driving genes in patients with advanced non-small cell lung carcinoma (NSCLC), especially in those whose cancer tissues are unavailable or in those that have acquired treatment resistance. Here, we describe a total of 119 patients with advanced EGFR-TKI-naive NSCLC and 15 EGFR-TKI-resistant patients to identify somatic SNVs, small indels, CNVs and gene fusions in 508 tumor-related genes...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29079040/overall-survival-analysis-and-characterization-of-an-egfr-mutated-non-small-cell-lung-cancer-nsclc-population
#14
Filipa Aguiar, Gabriela Fernandes, Henrique Queiroga, José Carlos Machado, Luís Cirnes, Conceição Souto Moura, Venceslau Hespanhol
BACKGROUND: Patients with activating somatic mutations in the Epidermal Growth Factor Receptor (EGFR) have better clinical outcomes when treated with Tyrosine Kinase Inhibitors (TKI) over chemotherapy. However, the impact of the use of TKIs on overall survival outside clinical trials is not well established. OBJECTIVE: To characterize and analyze the overall survival of a Caucasian population with NSCLC and EGFR mutations. METHODS: A retrospective cohort analysis of patients with NSCLC screened for EGFR mutations (exons 18-21) between October 2009 and July 2013 was conducted...
October 24, 2017: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/29075127/egfr-with-tki-sensitive-mutations-in-exon-19-is-highly-expressed-and-frequently-detected-in-chinese-patients-with-lung-squamous-carcinoma
#15
Aadil Ahmed Memon, Haiping Zhang, Ye Gu, Qian Luo, Jiajun Shi, Zixin Deng, Jian Ma, Wei Ma
Recently, tyrosine kinase inhibitors (TKIs) have been recommended as a first-line treatment for advanced non-small cell lung cancer (NSCLC), significantly improving the treatment outcomes of lung adenocarcinoma patients with the EGFR mutation. However, the application of TKIs for lung squamous cell carcinoma (SCC), the second largest pathological subtype of NSCLC, remains controversial because available data for the EGFR mutation profile and frequency in SCC patients are limited. In this study, 89 bronchoscopic-biopsy specimens from Chinese SCC male patients were assayed for EGFR exon 19 mutation, using improved polymerase chain reaction-denature gel gradient electrophoresis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29069959/the-liquid-biopsy-a-tool-for-a-combined-diagnostic-and-theranostic-approach-for-care-of-a-patient-with-late-stage-lung-carcinoma-presenting-with-bilateral-ocular-metastases
#16
Linda Bouhlel, Véronique Hofman, Célia Maschi, Marius Ilié, Maryline Allégra, Charles-Hugo Marquette, Clarisse Audigier-Valette, Juliette Thariat, Paul Hofman
Liquid biopsies (LB) are used routinely in clinical practice in two situations for late stage non-small-cell lung cancer (NSCLC) patients, (i) at the initial diagnosis when looking for activating mutations in EGFR in the absence of analyzable tissue DNA and, (ii) during tumor progression on a tyrosine kinase inhibitor treatment to look for the resistance mutation T790M in EGFR. LB is not presently recommended in daily practice for the diagnosis of NSCLC. Areas covered: We report the diagnosis of a NSCLC in a patient with bilateral ocular metastases after detection of a deletion in exon 19 of EGFR when using plasma DNA...
November 2, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29068312/the-role-of-proteomic-testing-in-improving-prognosis-and-care-planning-quality-measures-for-lung-cancer
#17
Ray D Page, A Christine Argento, David B Nash, Alexandria Skoufalos, Eric S Schaefer
PURPOSE: The Oncology Care Model (OCM) is a payment model from the Centers for Medicare and Medicaid Services designed to reduce costs and improve quality in cancer care. Key components of quality for the OCM originate from the 13-component cancer care plan. We surveyed the literature to understand the value of prognosis in OCM-directed planning for non-small-cell lung cancer (NSCLC) care and to investigate how the results of a prognostic, proteomic biomarker test, the VeriStrat test, can help OCM-participating providers meet the specific quality measures...
September 2017: Managed Care
https://www.readbyqxmd.com/read/29067441/multiplex-picoliter-droplet-digital-pcr-for-quantitative-assessment-of-egfr-mutations-in-circulating-cell-free-dna-derived-from-advanced-non-small-cell-lung-cancer-patients
#18
Qian Yu, Fei Huang, Meilin Zhang, Haiying Ji, Shenchao Wu, Ying Zhao, Chunyan Zhang, Jiong Wu, Beili Wang, Baisheng Pan, Xin Zhang, Wei Guo
To explore the possible diagnostic value of liquid biopsy, two multiplex panels using picoliter-droplet digital polymerase chain reaction (ddPCR) were established to quantitatively assess the epidermal growth factor receptor (EGFR) mutations in cell‑free DNA (cfDNA) extracted from the plasma of advanced non‑small cell lung cancer (NSCLC) patients. Plasma samples derived from 22 patients with stage IIIB/IV NSCLC harboring EGFR mutations in matched tumor tissues confirmed by amplification refractory mutation system (ARMS) analysis were subjected to two multiplex ddPCR panels to assess the abundance of tyrosine kinase inhibitor (TKI) ‑sensitive (19DEL, L858R) and TKI‑resistant (T790 M) mutations...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29063948/uncommon-mutation-types-of-epidermal-growth-factor-receptor-and-response-to-egfr-tyrosine-kinase-inhibitors-in-chinese-non-small-cell-lung-cancer-patients
#19
Kaiyan Chen, Xiaoqing Yu, Haiyang Wang, Zhiyu Huang, Yanjun Xu, Lei Gong, Yun Fan
PURPOSE: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the standard therapy for advanced lung adenocarcinomas with common EGFR mutations. However, the efficacy of EGFR-TKIs in patients with uncommon EGFR mutations (other than exon 19 deletions or exon 21 L858R mutation) remains undetermined. METHODS: Seven hundred and fifty-five non-small cell lung cancer (NSCLC) patients with EGFR mutation analyses for TKI therapy were identified between October 2010 and December 2015 in East of China...
October 24, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29050366/the-resistance-mechanisms-and-treatment-strategies-for-egfr-mutant-advanced-non-small-cell-lung-cancer
#20
REVIEW
Wen-Zhao Zhong, Qing Zhou, Yi-Long Wu
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have been established as the standard therapy for EGFR-sensitizing mutant advanced non-small-cell lung cancer (NSCLC). However, patients ultimately develop resistance to these drugs. There are several mechanisms of both primary and secondary resistance to EGFR-TKIs. The primary resistance mechanisms include point mutations in exon 18, deletions or insertions in exon 19, insertions, duplications and point mutations in exon 20 and point mutation in exon 21 of EGFR gene...
September 19, 2017: Oncotarget
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