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https://www.readbyqxmd.com/read/28196634/objective-domain-specific-her2-measurement-in-uterine-and-ovarian-serous-carcinomas-and-its-clinical-significance
#1
Daniel E Carvajal-Hausdorf, Kurt A Schalper, Yalai Bai, Jonathan Black, Alessandro D Santin, David L Rimm
INTRODUCTION: HER2 overexpression/amplification is identified in up to 40% of uterine serous carcinomas (USC) and 10% of ovarian serous carcinomas (OSC). However, clinical trials using various HER2-targeted agents failed to show significant responses. FDA-approved HER2 assays target only the protein's intracellular domain (ICD) and not the extracellular domain (ECD). Previous quantitative studies in breast cancer by our group have shown that ICD of HER2 is expressed in some cases that do not express the HER2 ECD...
February 11, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28188446/treatment-options-for-egfr-t790m-negative-egfr-tyrosine-kinase-inhibitor-resistant-non-small-cell-lung-cancer
#2
Salvatore Corallo, Ettore D'Argento, Antonia Strippoli, Michele Basso, Santa Monterisi, Sabrina Rossi, Alessandra Cassano, Carlo M Barone
The introduction of first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib and afatinib) for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC) has dramatically improved patients' prognosis and quality of life (QoL). Unfortunately, after an initial and sometimes durable benefit from EGFR-TKI therapy, all patients with EGFR-mutant lung cancer eventually become resistant to the treatment and experience disease progression. In approximately 50% of these patients, genomic alterations in the EGFR kinase domain resulting in the mutant T790M are responsible for the resistance and this has led to the development of novel EGFR inhibitors active against mutant-T790M EGFR...
February 10, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28177428/monitoring-of-somatic-mutations-in-circulating-cell-free-dna-by-digital-pcr-and-next-generation-sequencing-during-afatinib-treatment-in-patients-with-lung-adenocarcinoma-positive-for-egfr-activating-mutations
#3
E Iwama, K Sakai, K Azuma, T Harada, D Harada, K Nosaki, K Hotta, F Ohyanagi, T Kurata, T Fukuhara, H Akamatsu, K Goto, T Shimose, J Kishimoto, Y Nakanishi, K Nishio, I Okamoto
No abstract text is available yet for this article.
January 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28169392/afatinib-versus-gefitinib-in-patients-with-egfr-mutation-positive-advanced-non-small-cell-lung-cancer-overall-survival-data-from-the-phase-iib-lux-lung-7-trial
#4
L Paz-Ares, E-H Tan, K O'Byrne, L Zhang, V Hirsh, M Boyer, J C-H Yang, T Mok, K H Lee, S Lu, Y Shi, D H Lee, J Laskin, D-W Kim, S A Laurie, K Kölbeck, J Fan, N Dodd, A Märten, K Park
No abstract text is available yet for this article.
February 7, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28167215/treatments-for-egfr-mutant-non-small-cell-lung-cancer-nsclc-the-road-to-a-success-paved-with-failures
#5
REVIEW
Dae Ho Lee
The discovery of epidermal growth factor receptor (EGFR) activating mutations in non-small cell lung cancer (NSCLC) and the success story of EGFR tyrosine kinases inhibitors (TKIs) has changed the paradigm of cancer therapy from empirical cytotoxic chemotherapy to molecular-targeted cancer therapy. As a result, EGFR TKI therapy, including gefitinib, erlotinib and afatinib, has become the standard therapy for NSCLC patients with EGFR activating mutation as first-line therapy. However, most patients inevitably progress despite initial dramatic and rapid response to EGFR TKIs and therefore during the last decade, a lot of efforts have been made to identify and overcome various resistance mechanisms...
February 3, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28156651/oams-at-the-end-the-end-of-the-beginning-or-the-beginning-of-the-end
#6
Barbara Marie Galligan, Chintan Shah, Iris Chen Zhao, Brian Paciotti, Nathan Fairman, Quy Tran
: 229 Background: In 2001, after three months of review, the FDA approved the oral anticancer agent imatinib, making it the fastest approval in FDA history. Since then, the FDA has approved over 40 oral anti-cancer medications (OAMs) and the number continues to rise, transforming cancer care, improving survival in specific cancers and providing new hope. However, the rapid development of OAMs has produced uncertainty over the best use of these new medications, particularly at the end of life...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152932/national-comprehensive-cancer-network-petitions-submissions-and-outcomes
#7
Dinah Faith Huff, William J Hrushesky, Charles Lee Bennett, Kevin Knopf, Michael Baum
: 248 Background: The National Comprehensive Cancer Network (NCCN) invites petitions to its scientific panels. Most ( > 95%) are from the pharmaceutical industry lobbying to include their products in the NCCN Guidelines. Rarely, physicians request scientific scrutiny of the guidelines. We report the experience of Oncology Analytics (OA) with petition submissions and the possible impact on guidelines. METHODS: From 2011-2015, OA made 7 petitions to NCCN. The content of each was tracked into subsequent NCCN Guidelines to ascertain whether any changes resulted...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152720/comparison-of-real-world-acute-care-interventions-aci-in-patients-pts-with-advanced-non-small-cell-lung-cancer-adv-nsclc-treated-with-chemotherapy-versus-targeted-therapies
#8
Beata Korytowsky, Menaka Bhor, Ken Tuell, Bruce A Feinberg
: 37 Background: This analysis compared the frequency of ACI for any cause (emergency room [ER] visits, hospitalizations, and readmissions) to better understand the burden of treatment in adv NSCLC pts treated with chemotherapy (chemo) vs targeted therapy (TT). METHODS: Using Inovalon's MORE(2) Registry claims data, adv NSCLC pts treated with antineoplastics identified by ICD-9 codes from July 2013-2014 were selected. Inclusion: pts >18 y who received first-line (1L) systemic therapy within 6 mo of diagnosis...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152547/neratinib-resistance-and-cross-resistance-to-other-her2-targeted-drugs-due-to-increased-activity-of-metabolism-enzyme-cytochrome-p4503a4
#9
Susan Breslin, Michelle C Lowry, Lorraine O'Driscoll
BACKGROUND: Neratinib is in Phase 3 clinical trials but, unfortunately, the development of resistance is inevitable. Here, we investigated the effects of acquired neratinib resistance on cellular phenotype and the potential mechanism of this resistance. METHODS: Neratinib-resistant variants of HER2-positive breast cancer cells were developed and their cross-resistance investigated using cytotoxicity assays. Similarly, sensitivity of trastuzumab-resistant and lapatinib-resistant cells to neratinib was assessed...
February 2, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28149764/third-generation-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-in-t790m-positive-non-small-cell-lung-cancer-review-on-emerged-mechanisms-of-resistance
#10
REVIEW
Roberta Minari, Paola Bordi, Marcello Tiseo
Osimertinib, third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been approved in the US and EU for the treatment of EGFR mutant T790M-positive non-small cell lung cancer (NSCLC) patients resistant to first- or second-generation EGFR-TKIs, such as gefitinib, erlotinib and afatinib. Although exciting survival data and response rates have been registered in patients treated with this and other third-generation EGFR-TKIs, unfortunately acquired resistance still occurs after approximately 10 months...
December 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28149752/epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-for-the-treatment-of-central-nervous-system-metastases-from-non-small-cell-lung-cancer-the-present-and-the-future
#11
REVIEW
Claudia Proto, Martina Imbimbo, Rosaria Gallucci, Angela Brissa, Diego Signorelli, Milena Vitali, Marianna Macerelli, Giulia Corrao, Monica Ganzinelli, Francesca Gabriella Greco, Marina Chiara Garassino, Giuseppe Lo Russo
Lung cancer is one of the major causes of cancer related mortality worldwide. Brain metastases (BM) complicate clinical evolution of non-small cell lung cancer (NSCLC) in approximately 25-40% of cases, adversely influencing quality of life (QoL) and overall survival (OS). Systemic therapy remains the standard strategy for metastatic disease. Nevertheless, the blood-brain barrier (BBB) makes central nervous system (CNS) a sanctuary site. To date, the combination of chemotherapy with whole brain radiation therapy (WBRT), surgery and/or stereotactic radiosurgery (SRS) represents the most used treatment for patients (pts) with intracranial involvement...
December 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28149745/afatinib-induced-severe-esophagitis-in-a-lung-cancer-patient-with-an-activated-epidermal-growth-factor-receptor-mutation-a-case-report
#12
Takako Inoue, Madoka Kimura, Motohiro Tamiya, Kazumi Nishino, Toru Kumagai, Fumio Imamura
A 58-year-old woman with lung cancer complaint odynophagia by sour food. Endoscopic examination revealed severe erosion strictly limited to the esophagus. Drug-induced esophagitis was suspected. She was taking afatinib, loxoprofen, pregabalin, lorazepam, a formulation of butyric acid bacteria, and amino acid supplements for more than 1 month at the time of developing esophagitis. Her appetite was very poor for several days before developing the esophagitis. Although not definitive, the most probable cause of her esophagitis is an increased blood concentration of afatinib due to prolonged starved condition...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28138934/novel-egfr-inhibitors-in-non-small-cell-lung-cancer-current-status-of-afatinib
#13
REVIEW
Bin-Chi Liao, Chia-Chi Lin, James Chih-Hsin Yang
Afatinib, a second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been approved worldwide as a first-line treatment for advanced non-small cell lung cancer (NSCLC) that harbors activating EGFR mutations. Here, we have reviewed the recent clinical developments in the treatment of lung cancer using afatinib. Emerging data have revealed the overall survival benefit of first-line afatinib therapy in patients with advanced EGFR (del19)-positive NSCLC. Phase III studies of afatinib have shown the effectiveness of afatinib as a second-line treatment for advanced lung squamous cell carcinoma, as well as the benefit of continuing afatinib therapy in combination with cytotoxic chemotherapy for advanced NSCLC after the occurrence of disease progression in patients who are receiving afatinib monotherapy...
January 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28123721/toxicity-profile-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-in-patients-with-epidermal-growth-factor-receptor-gene-mutation-positive-lung-cancer
#14
Masayuki Takeda, Kazuhiko Nakagawa
Recent progress in the research on the molecular biology of lung cancer revealed that the clinical response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is associated with the presence of activating EGFR mutations. Three EGFR-TKIs, namely afatinib, erlotinib and gefitinib, are currently available for the treatment of patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC). Due to the dearth of published phase III trials prospectively evaluating the effects of one EGFR-TKI in comparison with another in such patients, the decision-making regarding which agent to recommend to any given patient lies with the treating physician...
January 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28115857/costs-of-adverse-events-associated-with-erlotinib-or-afatinib-in-first-line-treatment-of-advanced-egfr-positive-non-small-cell-lung-cancer
#15
Dolores Isla, Javier De Castro, Oscar Juan, Santiago Grau, Javier Orofino, Rocío Gordo, Carlos Rubio-Terrés, Darío Rubio-Rodríguez
OBJECTIVES: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are an established treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation. According to published meta-analyses, no significant efficacy differences have been demonstrated between erlotinib and afatinib. However, the incidence of EGFR-TKI-related adverse events (AEs) was lower with erlotinib. This study compares the cost of management of the AEs associated with these two drugs from the perspective of the Spanish National Health System (NHS)...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/28111428/randomized-phase-ii-study-of-afatinib-plus-simvastatin-versus-afatinib-alone-in-previously-treated-patients-with-advanced-non-adenocarcinomatous-non-small-cell-lung-cancer
#16
Youngjoo Lee, Ki Hyeong Lee, Geon Kook Lee, Soo-Hyun Lee, Kun Young Lim, Jungnam Joo, Yun Jung Go, Jin Soo Lee, Ji-Youn Han
Purpose: This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with non-adenocarcinomatous non-small cell lung cancer (NA-NSCLC). Materials and Methods: Patients with advanced NA-NSCLC who progressed after one or two chemotherapy regimens were randomly assigned to a simvastatin (40 mg/day) plus afatinib (40 mg/day) (AS) arm or to an afatinib (A) arm...
January 13, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28098949/identification-of-cellular-targets-involved-in-cardiac-failure-caused-by-pki-in-oncology-an-approach-combining-pharmacovigilance-and-pharmacodynamics
#17
E Patras de Campaigno, E Bondon-Guitton, G Laurent, F Montastruc, J L Montastruc, M Lapeyre-Mestre, F Despas
AIMS: To evaluate the risk of cardiac failure (CF) of 15 anticancer protein kinase inhibitors (PKIs) through a case/non-case analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. METHODS: To evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the WHO safety report database (VigiBase®). We realised a literature review to identify 21 PK possibly involved in CF caused by PKIs. Pearson's correlation coefficients (r) between aROR and affinity data of the 15 PKIs for the 21 PKs were calculated to identify the cellular target most likely involved in PKI-induced CF...
January 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28090532/afatinib-for-patients-with-epidermal-growth-factor-receptor-mutation-positive-non-small-cell-lung-cancer-clinical-implications-of-the-lux-lung-7-study
#18
COMMENT
Keunchil Park
No abstract text is available yet for this article.
December 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28089942/targeting-egfr-t790m-mutation-in-nsclc-from-biology-to-evaluation-and-treatment
#19
Antonio Passaro, Elena Guerini-Rocco, Alessia Pochesci, Davide Vacirca, Gianluca Spitaleri, Chiara Matilde Catania, Alessandra Rappa, Massimo Barberis, Filippo de Marinis
The identification of EGFR mutations and their respectively tyrosine kinase inhibitors (TKIs), changed dramatically treatment and survival of patients with EGFR-positive lung cancer. Nowadays, different EGFR TKIs as afatinib, erlotinib and gefitinib are approved worldwide for the treatment of NSCLC harbouring EGFR mutations, in particular exon 19 deletions or exon 21 (Leu858Arg) substitution EGFR mutations. In first-line setting, when comparing with platinum-based chemotherapy, these target drugs improves progression-free survival, response rate and quality of life...
January 12, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28088511/brief-report-egfr-l858m-l861q-cis-mutations-confer-selective-sensitivity-to-afatinib
#20
Jamie A Saxon, Lynette M Sholl, Pasi A Jänne
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with epidermal growth factor receptor (EGFR)-mutant lung cancers. However, the therapeutic efficacy of TKIs in patients with uncommon EGFR mutations remains unclear. METHODS: Next-generation sequencing was performed on a patient's lung adenocarcinoma tumor sample, revealing rare combined in cis (on the same allele) EGFR mutations. Stable Ba/F3 and NIH-3T3 cell lines harboring the mutations were established to investigate the effect of first, second, and third generation EGFR TKIs on cell proliferation by MTS assay and EGFR phosphorylation by Western blotting...
January 11, 2017: Journal of Thoracic Oncology
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