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Egfr-tki treatment for lung cancer

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https://www.readbyqxmd.com/read/28625653/most-t790m-mutations-are-present-on-the-same-egfr-allele-as-activating-mutations-in-patients-with-non-small-cell-lung-cancer
#1
Noriko Hidaka, Eiji Iwama, Naoki Kubo, Taishi Harada, Kohta Miyawaki, Kentaro Tanaka, Isamu Okamoto, Eishi Baba, Koichi Akashi, Hiroyuki Sasaki, Yoichi Nakanishi
OBJECTIVES: The T790M and C797S mutations of the epidermal growth factor receptor gene (EGFR) confer resistance to first- and third-generation EGFR tyrosine kinase inhibitors (TKIs), respectively, in patients with non-small cell lung cancer (NSCLC) harboring activating mutations of EGFR. C797S has been identified in cis or in trans with T790M in tumor specimens from patients who experienced treatment failure with first- and third-generation EGFR-TKIs. The allelic relation between T790M and activating mutations of EGFR has not been well characterized, however...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28623122/a-randomized-phase-ii-study-comparing-nivolumab-with-carboplatin-pemetrexed-for-patients-with-egfr-mutation-positive-nonsquamous-non-small-cell-lung-cancer-who-acquire-resistance-to-tyrosine-kinase-inhibitors-not-due-to-a-secondary-t790m-mutation-rationale
#2
Hidetoshi Hayashi, Yasutaka Chiba, Kazuko Sakai, Tomonobu Fujita, Hiroshige Yoshioka, Daisuke Sakai, Chiyoe Kitagawa, Tateaki Naito, Koji Takeda, Isamu Okamoto, Tetsuya Mitsudomi, Yutaka Kawakami, Kazuto Nishio, Shinichiro Nakamura, Nobuyuki Yamamoto, Kazuhiko Nakagawa
Antibodies to programmed cell death-1 (PD-1), such as nivolumab, have shown promising clinical activity in patients with advanced non-small-cell lung cancer (NSCLC), but their efficacy appears to be less pronounced in patients with such tumors harboring epidermal growth factor receptor gene (EGFR) mutations. Recent findings suggest that patients with EGFR mutation-positive NSCLC who develop resistance to tyrosine kinase inhibitors (TKIs) due to mechanisms other than acquisition of the secondary T790M mutation of EGFR are more likely to benefit from nivolumab treatment, possibly as a result of a higher level of expression of the PD-1 ligand PD-L1, than are patients who are T790M-positive...
May 25, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28620690/acquired-resistance-to-erlotinib-in-egfr-mutation-positive-lung-adenocarcinoma-among-hispanics-clicap
#3
Andrés F Cardona, Oscar Arrieta, Martín Ignacio Zapata, Leonardo Rojas, Beatriz Wills, Noemí Reguart, Niki Karachaliou, Hernán Carranza, Carlos Vargas, Jorge Otero, Pilar Archila, Claudio Martín, Luis Corrales, Mauricio Cuello, Carlos Ortiz, Luis E Pino, Rafael Rosell, Zyanya Lucia Zatarain-Barrón
BACKGROUND: Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. OBJECTIVE: The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression. PATIENTS AND METHODS: EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015...
June 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28607578/osimertinib-in-patients-with-advanced-epidermal-growth-factor-receptor-t790m-mutation-positive-non-small-cell-lung-cancer-rationale-evidence-and-place-in-therapy
#4
REVIEW
Biagio Ricciuti, Sara Baglivo, Luca Paglialunga, Andrea De Giglio, Guido Bellezza, Rita Chiari, Lucio Crinò, Giulio Metro
The identification of epidermal growth factor receptor (EGFR) mutations represented a fundamental step forward in the treatment of advanced non-small cell lung cancer (NSCLC) as they define a subset of patients who benefit from the administration of specifically designed targeted therapies. The inhibition of mutant EGFR through EGFR-tyrosine kinase inhibitors (TKIs), either reversible, first-generation gefitinib and erlotinib, or irreversible, second-generation afatinib, has dramatically improved the prognosis of patients harboring this specific genetic alteration, leading to unexpected clinical benefit...
June 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28599445/comparison-of-the-effectiveness-of-erlotinib-gefitinib-and-afatinib-for-treatment-of-non-small-cell-lung-cancer-in-patients-with-common-and-rare-egfr-gene-mutations
#5
Pawel Krawczyk, Dariusz M Kowalski, Rodryg Ramlau, Ewa Kalinka-Warzocha, Kinga Winiarczyk, Katarzyna Stencel, Tomasz Powrózek, Katarzyna Reszka, Kamila Wojas-Krawczyk, Maciej Bryl, Magdalena Wójcik-Superczyńska, Maciej Głogowski, Aleksander Barinow-Wojewódzki, Janusz Milanowski, Maciej Krzakowski
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are routinely used to treat non-small cell lung cancer (NSCLC) in patients with common activating mutations of the EGFR gene. The aim of the study was to compare the efficacies of EGFR-TKIs in patients with common (exon 19 deletions and exon 21 p.Leu858Arg) and rare EGFR mutations. A retrospective analysis of 180 NSCLC patients with common (n=167) and rare (n=13) EGFR mutations treated with erlotinib (n=98), gefitinib (n=66) and afatinib (n=16) was performed...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28599309/marsdenia-tenacissima-extract-overcomes-axl-and-met-mediated-erlotinib-and-gefitinib-cross-resistance-in-non-small-cell-lung-cancer-cells
#6
Shu-Yan Han, Wei Zhao, Hai-Bo Han, Hong Sun, Dong Xue, Yan-Na Jiao, Xi-Ran He, Shan-Tong Jiang, Ping-Ping Li
Tyrosine kinase inhibitors (TKIs) are an effective treatment strategy for non-small cell lung cancer (NSCLC) patients harboring mutations that result in constitutive activation of the epidermal growth factor receptor (EGFR). However, most patients eventually develop resistance to TKIs. This occurs due to additional EGFR mutations or the activation of bypass signaling pathways. In our previous work, we demonstrated that Marsdenia tenacissima extract (MTE) restored gefitinib sensitivity in resistant NSCLC cells with EGFR T790M or K-ras mutations...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28596108/association-between-egfr-t790m-status-and-progression-patterns-during-initial-egfr-tki-treatment-in-patients-harboring-egfr-mutation
#7
Yuko Oya, Tatsuya Yoshida, Hiroaki Kuroda, Junichi Shimizu, Yoshitsugu Horio, Yukinori Sakao, Yoshitaka Inaba, Toyoaki Hida, Yasushi Yatabe
BACKGROUND: Emergence of the T790M point mutation in exon 20 of the epidermal growth factor receptor (EGFR) is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). The aim of this study was to investigate the association between T790M mutation status and the progression patterns during EGFR-TKI treatment. METHODS: We reviewed 181 patients with advanced non-small-cell lung cancer harboring EGFR mutation, who were evaluated for T790M mutation status after initial EGFR-TKI failure (gefitinib, erlotinib, or afatinib)...
May 10, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28591695/efficacy-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-for-lung-squamous-carcinomas-harboring-egfr-mutation-a-multicenter-study-and-pooled-analysis-of-published-reports
#8
Yongmei Liu, Yan Zhang, Li Zhang, Bin Liu, Yongsheng Wang, Xiaojuan Zhou, Yanying Li, Qian Zhao, Youling Gong, Lin Zhou, Jiang Zhu, Zhenyu Ding, Jin Wang, Feng Peng, Meijuan Huang, Lu Li, Li Ren, You Lu
Epidermal growth factor receptor (EGFR) mutations are common in lung adenocarcinoma (ADC) but rare in squamous cell carcinoma (SQC). The efficacy of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) for SQC with EGFR mutations is unclear. The aim of this study was to evaluate the efficacy of EGFR-TKIs for these patients. We performed a retrospective matched-pair case-control study from 3 cancer centers, including 44 SQC and 44 ADC patients with EGFR mutation who were treated with EGFR-TKI. Subsequently, we performed a pooled analysis on the efficacy of EGFR-TKIs for EGFR-mutant SQC in 115 patients, including 71 patients selected from 25 published reports...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588734/plasma-t790m-and-hgf-as-potential-predictive-markers-for-egfr-tki-re-challenge
#9
Tomomi Nakamura, Naomi Watanabe, Akemi Sato, Kazutoshi Komiya, Hitomi Umeguchi, Toshiya Hosomi, Mitsuharu Hirai, Eisaburo Sueoka, Shinya Kimura, Naoko Sueoka-Aragane
Re-challenge with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) has been suggested to potentially improve survival in certain populations of patients with advanced lung cancer, but predictive markers for the success of EGFR-TKI re-challenge have not been identified. The present study analyzed 16 re-challenges with EGFR-TKI undertaken in 12 patients with lung adenocarcinoma by investigating T790M and hepatocyte growth factor (HGF) in plasma coupled with clinical characteristics. EGFR mutations in plasma DNA were detected using the wild inhibiting PCR and quenched probe system for exon 19 deletions, and T790M and L858R were detected using the mutation-biased PCR and quenched probe system...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28577957/egfr-t790m-mutation-testing-within-the-osimertinib-aura-phase-i-study
#10
Simon Dearden, Helen Brown, Suzanne Jenkins, Kenneth S Thress, Mireille Cantarini, Rebecca Cole, Malcolm Ranson, Pasi A Jänne
OBJECTIVES: Reliable epidermal growth factor receptor (EGFR) mutation testing techniques are required to identify eligible patients with EGFR mutation/T790M positive advanced non-small cell lung cancer (NSCLC), for treatment with osimertinib (AZD9291), an oral, potent, irreversible EGFR tyrosine kinase inhibitor (TKI) selective for EGFR-TKI-sensitizing and T790M resistance mutations over wild-type EGFR. There is no current consensus regarding the best method to detect EGFR T790M mutations...
July 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28565936/osimertinib-a-third-generation-tyrosine-kinase-inhibitor-for-treatment-of-epidermal-growth-factor-receptor-mutated-non-small-cell-lung-cancer-with-the-acquired-thr790met-mutation
#11
Meredith K Bollinger, Amanda S Agnew, Gerard P Mascara
Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for the treatment of metastatic EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) in patients failing previous TKI therapy. The T790M mutation is an acquired resistance mechanism found in over half of patients with NSCLC progressing on first-generation TKIs. First- and second-generation TKIs do not inhibit the T790M mutation at clinically relevant concentrations. Osimertinib is selective for mutated forms of EGFR, including the TKI-sensitizing mutations L858R and exon 19 deletions, as well as the acquired T790M resistance mutation...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28560038/mutational-status-predicts-the-risk-of-thromboembolic-events-in-lung-adenocarcinoma
#12
Elsa Davidsson, Nicola Murgia, Cristian Ortiz-Villalón, Emil Wiklundh, Magnus Sköld, Karl Gustav Kölbeck, Giovanni Ferrara
BACKGROUND: Precision medicine promises to improve prognosis of patients affected by untreatable diseases. Patients with lung cancer (especially lung adenocarcinoma) bear an increased risk of VTE. Mutations in the EGFR and rearrangement in the ALK genes identify specific subgroups of patients. Aim of this study was to investigate the role of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational status on the risk of venous thromboembolism (VTE) in lung adenocarcinoma...
2017: Multidisciplinary Respiratory Medicine
https://www.readbyqxmd.com/read/28555261/paradigm-shift-of-therapeutic-management-of-brain-metastases-in-egfr-mutant-non-small-cell-lung-cancer-in-the-era-of-targeted-therapy
#13
REVIEW
Akimasa Sekine, Hiroaki Satoh
Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations commonly present brain metastases (BM) at the time of NSCLC diagnosis or during the clinical course. Conventionally, the prognosis of BM has been extremely poor, but the advent of EGFR-tyrosine kinase inhibitors (TKIs) has drastically improved the prognosis in these patients. Despite the presence of the blood-brain barrier, EGFR-TKIs have dramatic therapeutic effects on both BM and extracranial disease. In addition, recent systemic chemotherapies reportedly play a role in controlling BM...
July 2017: Medical Oncology
https://www.readbyqxmd.com/read/28554755/characterization-of-common-and-rare-mutations-in-egfr-and-associated-clinicopathological-features-in-a-large-population-of-chinese-patients-with-lung-cancer
#14
Bing Wei, Pengfei Ren, Chengjuan Zhang, Zhizhong Wang, Bing Dong, Ke Yang, Jiuzhou Zhao, Shichun Tu, Jie Ma, Yongjun Guo
Lung cancer with EGFR mutation is often associated pathological characteristics and good responses to EGFR tyrosine kinase inhibitors (TKIs). However, certain types of rare EGFR mutations have be linked to cases with poor response to EGFR TKIs. Therefore, extensive molecular screening and pathological characterization are essential for accurate diagnosis and selection of effective treatment plans. Although a large body of studies have established the rate of EGFR mutations as a whole entity, the rates of each individual types of mutations, especially those rare ones, have not been precisely determined in large patient populations with uniform genetic background...
April 20, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28548967/detection-of-activating-and-acquired-resistant-mutation-in-plasma-from-egfr-mutated-nsclc-patients-by-peptide-nucleic-acid-pna-clamping-assisted-fluorescence-melting-curve-analysis
#15
Chang Gon Kim, Hyo Sup Shim, Min Hee Hong, Yoon Jin Cha, Su Jin Heo, Hyung Soon Park, Jee Hung Kim, Jin Gu Lee, Chang Young Lee, Byoung Chul Cho, Hye Ryun Kim
This study was designed to prospectively examine whether peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper™) is feasible for the detection of activating and acquired resistant epidermal growth factor receptor (EGFR) mutation in plasma. Patients with non-small cell lung cancer harboring activating EGFR mutations who were scheduled to undergo EGFR-tyrosine kinase inhibitors (EGFR-TKIs) were enrolled between September 2011 and March 2015. A total of 102 patients with EGFR-mutated lung cancer were enrolled, 53 had available plasma samples at disease progression, and 28 underwent serial plasma sampling during EGFR-TKI treatment...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28529628/cross-platform-comparison-of-four-leading-technologies-for-detecting-egfr-mutations-in-circulating-tumor-dna-from-non-small-cell-lung-carcinoma-patient-plasma
#16
Ting Xu, Xiaozheng Kang, Xiaofang You, Liang Dai, Dequan Tian, Wanpu Yan, Yongbo Yang, Hongchao Xiong, Zhen Liang, Grace Q Zhao, Shengrong Lin, Ke-Neng Chen, Guobing Xu
Analysis of circulating tumor DNA (ctDNA) is emerging as a powerful tool for guiding targeted therapy and monitoring tumor evolution in patients with non-small cell lung cancer (NSCLC), especially when representative tissue biopsies are not available. Here, we have compared the ability of four leading technology platforms to detect epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, T790M and G719X) in ctDNA from NSCLC patients. Two amplification refractory mutation systems (cobas-ARMS and ADx-ARMS), a droplet digital polymerase chain reaction (ddPCR) and a next-generation sequencing (Firefly NGS) platform were included in the comparison...
2017: Theranostics
https://www.readbyqxmd.com/read/28527899/egfr-mutation-analysis-for-prospective-patient-selection-in-two-phase-ii-registration-studies-of-osimertinib
#17
Suzanne Jenkins, James Chih-Hsin Yang, Pasi A Jänne, Kenneth S Thress, Karen Yu, Rachel Hodge, Susie Weston, Simon Dearden, Sabina Patel, Mireille Cantarini, Frances A Shepherd
INTRODUCTION: Osimertinib is an oral, CNS active, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of EGFR T790M-positive advanced non-small cell lung cancer (NSCLC). Here we evaluate EGFR mutation frequencies in two Phase II studies of osimertinib (AURA extension and AURA2). METHODS: Patients with EGFR mutation-positive advanced NSCLC provided tumor samples following progression on their latest line of therapy for mandatory central T790M testing for study selection criteria...
May 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28522592/sensitization-of-egfr-wild-type-non-small-cell-lung-cancer-cells-to-egfr-tyrosine-kinase-inhibitor-erlotinib
#18
Judith Raimbourg, Marie-Pierre Joalland, Mathilde Cabart, Ludmilla de Plater, Fanny Bouquet, Ariel Savina, Didier Decaudin, Jaafar Bennouna, François M Vallette, Lisenn Lalier
The benefit of EGFR-TKI in non-small cell lung cancer has been demonstrated in mutant EGFR tumors as first-line treatment but the benefit in wild-type EGFR tumors is marginal as well as restricted to maintenance therapy in pretreated patients. This work aimed at questioning the effects of cisplatin initial treatment on the EGFR pathway in non-small cell lung cancer and the functional consequences in vitro and in in vivo animal models of Patient-Derived Xenografts (PDX). We establish here that cisplatin pretreatment specifically sensitizes wild-type EGFR expressing cells to erlotinib, contrary to what happens in mutant-EGFR cells and with a blocking EGFR antibody, both in vitro and in vivo The sensitization entails the activation of the kinase Src upstream of EGFR, thereafter transactivating EGFR through a ligand-independent activation...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28515374/polyphyllin-i-overcomes-emt-associated%C3%A2-resistance%C3%A2-to-erlotinib-in-lung-cancer-cells-via-il-6-stat3-pathway-inhibition
#19
Wei Lou, Yan Chen, Ke-Ying Zhu, Huizi Deng, Tianhao Wu, Jun Wang
Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is the most important limiting factor for treatment efficiency in EGFR-mutant non-small cell lung cancer (NSCLC). Much work has linked the epithelial-mesenchymal transition (EMT) to the emergence of drug resistance, consequently, ongoing research has been focused on exploring the therapeutic options to reverse EMT for delaying or preventing drug resistance. Polyphyllin I (PPI) is a natural compound isolated from Paris polyphylla rhizomes and displayed anti-cancer properties...
May 18, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28503070/tyrosine-kinase-inhibitor-combination-therapy-in-first-line-treatment-of-non-small-cell-lung-cancer-systematic-review-and-network-meta-analysis
#20
Sarah Batson, Stephen A Mitchell, Ricarda Windisch, Elisabetta Damonte, Veronica C Munk, Noemi Reguart
INTRODUCTION: The introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved the outlook for patients with advanced non-small-cell lung cancer (NSCLC) with EGFR+ mutations. However, most patients develop resistance, with the result that median progression-free survival (PFS) iŝ12 months. Combining EGFR-TKIs with other agents, such as bevacizumab, is a promising approach to prolonging remission. This systematic review and network meta-analysis (NMA) were undertaken to assess available evidence regarding the benefits of first-line combination therapy involving EGFR-TKIs in patients with advanced NSCLC...
2017: OncoTargets and Therapy
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