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https://www.readbyqxmd.com/read/28631135/long-term-clinical-benefit-from-salvage-egfr-tyrosine-kinase-inhibitors-in-advanced-non-small-cell-lung-cancer-patients-with-egfr-wild-type-tumors
#1
F Koinis, A Voutsina, A Kalikaki, A Koutsopoulos, E Lagoudaki, E Tsakalaki, E K Dermitzaki, E Kontopodis, A G Pallis, V Georgoulias, A Kotsakis
BACKGROUND: Erlotinib has been approved for the management of NSCLC patients after failure of the first or subsequent line of chemotherapy. Although the efficacy of erlotinib is clearly associated with the presence of EGFR mutations, there is a subset of patients with EGFR wild-type (EGFRwt) tumors who impressively respond. PATIENTS AND METHODS: Patients with EGFRwt NSCLC who received salvage (≥2nd line) treatment with erlotinib for a prolonged period (>6 months), were sought from the database of the Hellenic Oncology Research Group...
June 19, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28629461/cost-effectiveness-of-lung-cancer-screening-and-treatment-methods-a-systematic-review-of-systematic-reviews
#2
Farbod Ebadifard Azar, Saber Azami-Aghdash, Fatemeh Pournaghi-Azar, Alireza Mazdaki, Aziz Rezapour, Parvin Ebrahimi, Negar Yousefzadeh
BACKGROUND: Due to extensive literature in the field of lung cancer and their heterogeneous results, the aim of this study was to systematically review of systematic reviews studies which reviewed the cost-effectiveness of various lung cancer screening and treatment methods. METHODS: In this systematic review of systematic reviews study, required data were collected searching the following key words which selected from Mesh: "lung cancer", "lung oncology", "lung Carcinoma", "lung neoplasm", "lung tumors", "cost- effectiveness", "systematic review" and "Meta-analysis"...
June 19, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28629454/impact-of-pharmacy-channel-on-adherence-to-oral-oncolytics
#3
Michael Stokes, Carolina Reyes, Yu Xia, Veronica Alas, Hans-Peter Goertz, Luke Boulanger
BACKGROUND: Oral chemotherapy is increasingly prescribed to treat cancer. Despite its benefits, concerns have been raised regarding adherence to therapy. The study objective was to compare and measure adherence, persistence, and abandonment in patients filling prescriptions in traditional retail (TR) versus specialty pharmacy (SP) channels. METHODS: Using a retrospective cohort design, we selected newly treated patients aged ≥18 years with a prescription for erlotinib, capecitabine, or imatinib during 2007-2011 from a Medco population of both United States commercial and Medicare health plans...
June 19, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28628631/computational-explanation-for-bioactivation-mechanism-of-targeted-anticancer-agents-mediated-by-cytochrome-p450s-a-case-of-erlotinib
#4
Chun-Zhi Ai, Yong Liu, Wei Li, De-Meng Chen, Xin-Xing Zhu, Ya-Wei Yan, Du-Chu Chen, Yi-Zhou Jiang
EGFR inhibitors, even with therapeutics superiorities in anticancer, can cause idiosyncratic pulmonary and hepatic toxicities that are associated with the reactive electrophile bioactivated by Cytochrome P450s (P450s). Until now, neither has the electrophilic intermediate been caught experimentally, nor has the subtle mechanism been declared. Herein, the underlying mechanism of bioactivation mediated by P450s was explored by DFT calculations for a case of EGFR inhibitor, Erlotinib. Based on the calculation and analysis, we suggest that with other metabolites, reactive electrophiles of Erlotinib: epoxide and quinine-imine, can be generated by several steps along the oxidative reaction pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28627678/bevacizumab-counteracts-vegf-dependent-resistance-to-erlotinib-in-an-egfr-mutated-nsclc-xenograft-model
#5
Chinami Masuda, Mieko Yanagisawa, Keigo Yorozu, Mitsue Kurasawa, Koh Furugaki, Nobuyuki Ishikura, Toshiki Iwai, Masamichi Sugimoto, Kaname Yamamoto
Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), shows superior efficacy in patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations (EGFR Mut+). However, almost all tumors eventually develop resistance to erlotinib. Recently, the Phase II JO25567 study reported significant prolongation of progression-free survival (PFS) by erlotinib plus bevacizumab combination compared with erlotinib in EGFR Mut+ NSCLC. Herein, we established a preclinical model which became refractory to erlotinib after long-term administration and elucidated the mode of action of this combination...
June 8, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28625657/synergy-between-next-generation-egfr-tyrosine-kinase-inhibitors-and-mir-34a-in-the-inhibition-of-non-small-cell-lung-cancer
#6
Jane Zhao, Adriana Guerrero, Kevin Kelnar, Heidi J Peltier, Andreas G Bader
OBJECTIVES: EGFR tyrosine kinase inhibitors (TKIs) are widely used to treat NSCLC, primarily patients with activating mutations, with more limited response in wild-type disease. However, even with EGFR-mutated disease, many patients fail to respond, most who initially respond fail to respond completely, and almost all develop resistance and inevitably progress. New therapeutic options that improve these outcomes could provide substantial clinical benefit. We previously demonstrated strong synergistic effects between erlotinib and the tumor suppressor microRNA miR-34a, sensitizing NSCLC cells with primary resistance (EGFR wild-type) and restoring sensitivity in cells with acquired resistance...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28625646/egfr-exon-18-dele709_t710insd-mutated-stage-iv-lung-adenocarcinoma-with-response-to-afatinib
#7
Uroosa Ibrahim, Amina Saqib, Jean Paul Atallah
Epidermal Growth Factor Receptor (EGFR) targetable mutations have changed the landscape for treatment of advanced stage non-small cell lung cancer in recent years. Three generations of tyrosine kinase inhibitors are now available to target cancers harboring these mutations. The most common EGFR mutations occur in Exons 19 and 21. Exon 18 mutations are extremely rare comprising of 4.1% of all EGFR mutations and the delE709_T710insD mutation accounts for only 0.16% of mutations when occurring as a sole mutation, however, the frequency can vary with the kit utilized for testing...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28625643/sequential-liquid-biopsies-reveal-dynamic-alterations-of-egfr-driver-mutations-and-indicate-egfr-amplification-as-a-new-mechanism-of-resistance-to-osimertinib-in-nsclc
#8
Franciele H Knebel, Fabiana Bettoni, Andrea K Shimada, Manoel Cruz, João Victor Alessi, Marcelo V Negrão, Luiz Fernando L Reis, Artur Katz, Anamaria A Camargo
Osimertinib is an EGFR-T790M-specific TKI, which has demonstrated impressive response rates in NSCLC, after failure to first-line anti-EGFR TKIs. However, acquired resistance to osimertinib is also observed and the molecular mechanisms of resistance are not yet fully understood. Monitoring and managing NSCLC patients who progressed on osimertinib is, therefore, emerging as an important clinical challenge. Sequential liquid biopsies were used to monitor a patient with EGFR-exon19del positive NSCLC, who received erlotinib and progressed through the acquisition of the EGFR-T790M mutation...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28625641/emergence-of-novel-and-dominant-acquired-egfr-solvent-front-mutations-at-gly796-g796s-r-together-with-c797s-r-and-l792f-h-mutations-in-one-egfr-l858r-t790m-nsclc-patient-who-progressed-on-osimertinib
#9
Sai-Hong Ignatius Ou, Jean Cui, Alexa B Schrock, Michael E Goldberg, Viola W Zhu, Lee Albacker, Philip J Stephens, Vincent A Miller, Siraj M Ali
Acquired epidermal growth factor receptor (EGFR) resistance mutations to osimertinib are common, including the EGFR C797S that abolishes the covalent binding of osimertinib to EGFR. Here we report the emergence of novel EGFR solvent front mutations at Gly796 (G796S/R) in addition to a hinge pocket L792F/H mutations, and C797S/G all in cis with T790M in a single patient on progression on osimertinib as detected by plasma circulating tumor DNA (ctDNA) assay in the course of clinical care. A 69-year-old Caucasian female former light-smoker presented with stage IV EGFR L858R positive adenocarcinoma who developed EGFR T790M mutation after 8 month treatment of erlotinib...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28625629/a-phase-ib-trial-of-continuous-once-daily-oral-afatinib-plus-sirolimus-in-patients-with-epidermal-growth-factor-receptor-mutation-positive-non-small-cell-lung-cancer-and-or-disease-progression-following-prior-erlotinib-or-gefitinib
#10
Teresa Moran, Ramón Palmero, Mariano Provencio, Amelia Insa, Margarita Majem, Noemí Reguart, Joaquim Bosch-Barrera, Dolores Isla, Enric Carcereny Costa, Chooi Lee, Marta Puig, Sandrine Kraemer, David Schnell, Rafael Rosell
OBJECTIVES: Dysregulation of the downstream PI3K/AKT/mTOR signaling pathway is a proposed mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). We investigated safety and antitumor activity of afatinib plus sirolimus as a potential combination to reverse acquired resistance to EGFR-TKIs in a phase IB trial in patients with EGFR mutation-positive non-small-cell lung cancer (EGFR mut NSCLC) and/or disease progression following prior erlotinib/gefitinib...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28625621/patterns-of-initial-and-intracranial-failure-in-metastatic-egfr-mutant-non-small-cell-lung-cancer-treated-with-erlotinib
#11
Suchit H Patel, Andreas Rimner, Amanda Foster, Zhigang Zhang, Kaitlin M Woo, Helena A Yu, Gregory J Riely, Abraham J Wu
OBJECTIVES: Patients with metastatic EGFR-mutant (mEGFRmt) NSCLC have favorable survival when treated with erlotinib. We hypothesized that treatment failure in most patients is limited to initial sites of disease, in which case incorporating local therapy such as radiation might further delay progression. We therefore analyzed patterns and predictors of failure in a large cohort of such patients. MATERIALS AND METHODS: We reviewed 189 patients treated with erlotinib for mEGFRmt NSCLC...
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
#12
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
#13
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/28617069/simultaneous-determination-of-six-tyrosine-kinase-inhibitors-in-human-plasma-using-hplc-q-orbitrap-mass-spectrometry
#14
Mao-Wei Ni, Jie Zhou, Hui Li, Wei Chen, Han-Zhou Mou, Zhi-Guo Zheng
AIM: Gefitinib, erlotinib, icotinib, crizotinib, lapatinib and apatinib are targeted cancer therapy agents acting through inhibition of tyrosine kinase. Method for quantifying these six drugs in human plasma of patients was required. MATERIALS & METHODS: An HPLC-Q-Orbitrap method (based on HPLC-MS/MS) was developed and validated for the simultaneous detection and quantitation of six tyrosine kinase inhibitors in human plasma. Sample was extracted by liquid-liquid extraction (ethyl acetate: tert-Butyl methyl ether, 1:1 v/v)...
June 15, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28616379/re-biopsy-after-relapse-of-targeted-therapy-t790m-after-epidermal-growth-factor-mutation-where-and-why-based-on-a-case-series
#15
Paul Zarogoulidis, Aggeliki Rapti, Chrysanthi Sardeli, Panagiotis Chinelis, Anastasia Athanasiadou, Katerina Paraskevaidou, Anastasios Kallianos, Lemonia Veletza, Georgia Trakada, Wolfgang Hohenforst-Schmidt, Haidong Huang
Guidelines for the treatment of non-small cell lung cancer adenocarcinoma positive in epidermal growth factor mutations indicate tyrosine kinase inhibitors. There are currently three tyrosine kinase inhibitors that can be used as first line treatment: gefitinib, erlotinib and afatinib. Regarding erlotinib and afatinib dosage can be modified in the case of severe adverse effects. In the case of disease relapse investigation for T790M mutation has to be made either with re-biopsy or liquid biopsy and osimertinib has to be administered when T790M is diagnosed...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28614784/erlotinib-based-doublet-targeted-therapy-versus-erlotinib-alone-in-previously-treated-advanced-non-small-cell-lung-cancer-a-meta-analysis-from-24-randomized-controlled-trials
#16
REVIEW
Jian-Wei Gao, Ping Zhan, Xiang-Yu Qiu, Jia-Jia Jin, Tang-Feng Lv, Yong Song
BACKGROUND: To assess the efficacy profile of erlotinib-based doublet targeted therapy compared with erlotinib monotherapy for previously treated patients with advanced NSCLC, a meta-analysis was performed. PATIENTS AND METHODS: We rigorously searched PubMed, Embase, Cochrane and meeting proceedings. Phase II/III randomized trials reporting on the efficacy of erlotinib-doublet therapy versus single-agent therapy were selected. We estimated the HR for OS, PFS and the RR for ORR, DCR, 1-year SR...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611289/next-generation-sequencing-and-molecular-imaging-identify-egfr-mutation-and-amplification-in-a-glioblastoma-multiforme-patient-treated-with-an-egfr-inhibitor-a-case-report
#17
Ke Zhou, Hui Yao, Xuewen Zhang, Jiangang Liu, Zhenyu Qi, Xueshun Xie, Xiaoting Xu, Youxin Zhou, Zhengquan Yu, Zhong Wang, Yanjun Che, Yulun Huang
Epidermal growth factor receptor (EGFR) mutations and amplifications are frequently reported in glioblastoma multiforme (GBM) patients. In this case report, we utilize next-generation sequencing (NGS) and EGFR molecular imaging to investigate intratumoral heterogeneity in a male patient presenting with GBM. Further, we describe the patient's clinical course as well as outcomes of targeted EGFR therapy with erlotinib, an EGFR tyrosine kinase inhibitor (TKI). NGS demonstrated the presence of an EGFR mutation and amplification in our patient...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28607607/microrna-signature-of-lung-adenocarcinoma-with-egfr-exon-19-deletion
#18
Lixia Ju, Mingquan Han, Xuefei Li, Chao Zhao
The findings of EGFR mutations and the development of targeted therapies have significantly improved the overall survival of lung cancer patients. Still, the prognosis remains poor, so we need to know more about the genetic alterations in lung cancer. MicroRNAs are dysregulated in lung cancer, and some of them can regulate EGFR. So it is very important to predict the candidate microRNAs that target mutated EGFR and to investigate the role of these candidate microRNAs in lung cancer. In this study, we investigated the difference of microRNAs expression between lung adenocarcinoma cell lines with EGFR exon 19 deletion (H1650 and PC9) and wild-type (H1299 and A549) using the Phalanx Human Whole Genome Microarray...
2017: Journal of Cancer
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
#19
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/28606519/folate-conjugated-thermosensitive-o-maleoyl-modified-chitosan-micellar-nanoparticles-for-targeted-delivery-of-erlotinib
#20
Marziyeh Fathi, Parham Sahandi Zangabad, Ayuob Aghanejad, Jaleh Barar, Hamid Erfan-Niya, Yadollah Omidi
In the present work, new self-assembled nanoparticles (NPs) were engineered using biocompatible and biodegradable natural polymer, chitosan (CS). The complexation of CS with sodium dodecyl sulfate (SDS) facilitated the regioselective chemical modification of CS hydroxyl groups with maleic anhydride, and produced polymerizable precursor of CS that was further grafted with N-isopropylacrylamide (NIPAAm) as temperature-sensitive moiety and oleic acid (OA) as hydrophobic monomer. After removal of SDS complex, the free amino groups were functionalized with folic acid (FA) to form folate-(PNIPAAm-co-OA)-g-CS micellar NPs...
September 15, 2017: Carbohydrate Polymers
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