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Nsclc clinical trials

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https://www.readbyqxmd.com/read/28327923/heart-dose-exposure-as-prognostic-marker-after-radiotherapy-for-resectable-stage-iiia-b-non-small-cell-lung-cancer-secondary-analysis-of-a-randomised-trial
#1
M Guberina, W Eberhardt, M Stuschke, T Gauler, F Heinzelmann, D Cheufou, M Kimmich, G Friedel, H Schmidberger, K Darwiche, V Jendrossek, M Schuler, G Stamatis, C Pöttgen
BACKGROUND: Heart exposure to ionizing irradiation can cause ischemic heart disease. The partial heart volume receiving ≥5 Gy (heartV5) was supposed to be an independent prognostic factor for survival after radiochemotherapy for locally advanced non-small cell lung cancer (NSCLC). But validation of the latter hypothesis is needed under the concurrent risks of lung cancer patients. PATIENTS AND METHODS: The ESPATUE phase III trial recruited patients with potentially operable IIIA(N2)/selected IIIB NSCLC between 01/2004 and 01/2013...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28319809/abt-737-synergizes-with-cisplatin-bypassing-aberration-of-apoptotic-pathway-in-non-small-cell-lung-cancer
#2
Eun Young Kim, Ji Ye Jung, Arum Kim, Yoon Soo Chang, Se Kyu Kim
A subset of non-small cell lung cancer (NSCLC), which does not have a druggable driver mutation, is treated with platinum-based cytotoxic chemotherapy, but it develops resistance triggered by DNA damage responses. Here, we investigated the effect of activation of STAT3 by cisplatin on anti-apoptotic proteins and the effectiveness of a co-treatment with cisplatin and a BH3 mimetic, ABT-737. We analyzed the relationship between cisplatin and STAT3 pathway and effect of ABT-737, when combined with cisplatin in NSCLC cells and K-ras mutant mouse models...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28303491/changing-the-therapeutic-landscape-in-non-small-cell-lung-cancers-the-evolution-of-comprehensive-molecular-profiling-improves-access-to-therapy
#3
REVIEW
Joshua K Sabari, Fernando Santini, Isabella Bergagnini, W Victoria Lai, Kathryn C Arbour, Alexander Drilon
Targeting genomic alterations has led to a paradigm shift in the treatment of patients with lung cancer. In an effort to better identify potentially actionable alterations that may predict response to FDA-approved and or investigational therapies, many centers have migrated towards performing targeted exome sequencing in patients with stage IV disease. The implementation of next-generation sequencing (NGS) in the evaluation of tumor tissue from patients with NSCLC has led to the discovery of targetable alterations in tumors that previously had no known actionable targets by less comprehensive profiling...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28293555/second-line-treatment-of-non-small-cell-lung-cancer-clinical-pathological-and-molecular-aspects-of-nintedanib
#4
REVIEW
Luis Corrales, Amanda Nogueira, Francesco Passiglia, Angela Listi, Christian Caglevic, Marco Giallombardo, Luis Raez, Edgardo Santos, Christian Rolfo
Lung carcinoma is the leading cause of death by cancer in the world. Nowadays, most patients will experience disease progression during or after first-line chemotherapy demonstrating the need for new, effective second-line treatments. The only approved second-line therapies for patients without targetable oncogenic drivers are docetaxel, gemcitabine, pemetrexed, and erlotinib and for patients with target-specific oncogenes afatinib, osimertinib, crizotinib, alectinib, and ceritinib. In recent years, evidence on the role of antiangiogenic agents have been established as important and effective therapeutic targets in non-small cell lung cancer (NSCLC)...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28293124/spotlight-on-necitumumab-in-the-treatment-of-non-small-cell-lung-carcinoma
#5
REVIEW
Manish K Thakur, Antoinette J Wozniak
The treatment options for metastatic non-small-cell lung cancer (NSCLC) have expanded dramatically in the last 10 years with the discovery of newer drugs and targeted therapy. Epidermal growth factor receptor (EGFR), when aberrantly activated, promotes cell growth and contributes in various ways to the malignant process. EGFR has become an important therapeutic target in a variety of malignancies. Small-molecule tyrosine kinase inhibitors (TKIs) of EGFR are being used to treat advanced NSCLC and are particularly effective in the presence of EGFR mutations...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28287730/discovery-of-n-3r-4r-4-fluoro-1-6-3-methoxy-1-methyl-1h-pyrazol-4-yl-amino-9-methyl-9h-purin-2-yl-pyrrolidine-3-yl-acrylamide-pf-06747775-through-structure-based-drug-design-a-high-affinity-irreversible-inhibitor-targeting-oncogenic-egfr-mutants-with-selectivity
#6
Simon Planken, Douglas Carl Behenna, Sajiv K Nair, Theodore Otto Johnson, Asako Nagata, Chau Almaden, Simon Bailey, T Eric Ballard, Louise Bernier, Hengmiao Cheng, Sujin Cho-Schultz, Deepak Dalvie, Judith G Deal, Dac M Dinh, Martin P Edwards, Rose Ann Ferre, Ketan S Gajiwala, Michelle D Hemkens, Robert S Kania, John C Kath, Jean Matthews, Brion W Murray, Sherry Niessen, Suvi T M Orr, Mason Pairish, Neal W Sach, Hong Shen, Manli Shi, James Solowiej, Khanh Tran, Elaine Tseng, Paolo Vicini, Yuli Wang, Scott L Weinrich, Ru Zhou, Michael Zientek, Longqing Liu, Yiqin Luo, Shuibo Xin, Chengyi Zhang, Jennifer Anne Lafontaine
Mutant epidermal growth factor receptor (EGFR) is a major driver of non-small cell lung cancer (NSCLC). Marketed first generation inhibitors, such as erlotinib, effect a transient beneficial response in EGFR-mutant NSCLC patients before resistance mechanisms render these inhibitors ineffective. Secondary oncogenic EGFR mutations account for approximately 50% of relapses, the most common being the gatekeeper T790M substitution that renders existing therapies ineffective. The discovery of PF-06459988 (1), an irreversible pyrrolopyrimidine inhibitor of EGFR T790M mutants was recently disclosed1...
March 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28285684/dual-occurrence-of-alk-g1202r-solvent-front-mutation-and-small-cell-lung-cancer-transformation-as-resistance-mechanisms-to-second-generation-alk-inhibitors-without-prior-exposure-to-crizotinib-pitfall-of-solely-relying-on-liquid-re-biopsy
#7
Sai-Hong Ignatius Ou, Thomas K Lee, Lauren Young, Maria Y Fernandez-Rocha, Dean Pavlick, Alexa B Schrock, Viola W Zhu, Jeffrey Milliken, Siraj M Ali, Barbara J Gitlitz
Development of the acquired ALK G1202R solvent front mutation and small cell lung cancer (SCLC) transformation have both been independently reported as resistance mechanisms to ALK inhibitors in ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients but have not been reported in the same patient. Here we report an ALK+ NSCLC patient who had disease progression after ceritinib and then alectinib where an ALK G1202R mutation was detected on circulating tumor (ct) DNA prior to enrollment onto a trial of another next generation ALK inhibitor, lorlatinib...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28285682/pretreatment-neutrophil-to-lymphocyte-ratio-as-a-marker-of-outcomes-in-nivolumab-treated-patients-with-advanced-non-small-cell-lung-cancer
#8
Stephen J Bagley, Shawn Kothari, Charu Aggarwal, Joshua M Bauml, Evan W Alley, Tracey L Evans, John A Kosteva, Christine A Ciunci, Peter E Gabriel, Jeffrey C Thompson, Susan Stonehouse-Lee, Victoria E Sherry, Elizabeth Gilbert, Beth Eaby-Sandy, Faith Mutale, Gloria DiLullo, Roger B Cohen, Anil Vachani, Corey J Langer
OBJECTIVES: Efficient use of nivolumab in non-small-cell lung cancer (NSCLC) has been limited by the lack of a definitive predictive biomarker. In patients with metastatic melanoma treated with ipilimumab, a pretreatment neutrophil-to-lymphocyte ratio (NLR)<5 has been associated with improved survival. This retrospective cohort study aimed to determine whether the pretreatment NLR was associated with outcomes in NSCLC patients treated with nivolumab. METHODS: We reviewed the medical records of all patients with previously treated advanced NSCLC who received nivolumab between March 2015 and March 2016 outside of a clinical trial at the University of Pennsylvania...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28280362/sequential-treatment-of-tyrosine-kinase-inhibitor-and-platinum-based-doublet-chemotherapy-on-egfr-mutant-non-small-cell-lung-cancer-a-meta-analysis-of-randomized-controlled-clinical-trials
#9
Lifen Qiao, Jin Wang, Guoxian Long, Yueqiang Jiang
There is debate surrounding which treatment is superior in overall survival (OS) rates in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC); first-line tyrosine kinase inhibitor (TKI) followed by second-line platinum-based doublet chemotherapy (PCT), or the reverse sequence. Cross treatment of first- and second-line TKI and PCT makes it difficult to deduce which sequence (TKI-PCT or PCT-TKI) is better for OS. Using the keywords "lung cancer" and "EGFR" we identified clinical trials within the PubMed database which were published between January 2006 and November 2016...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28276858/the-safety-of-second-line-treatment-options-for-non-small-cell-lung-cancer
#10
Antonio Rossi, Paolo Maione, Giuseppe Santabarbara, Paola Claudia Sacco, Francesca Casaluce, Assunta Sgambato, Maria Luisa Barzelloni, Giovanni Palazzolo, Cesare Gridelli
Non-small-cell lung cancer (NSCLC) patients after first-line therapy ultimately suffer progression. At this time, many patients still have a good performance status and can be considered for further active treatment. Two chemotherapeutic agents, docetaxel and pemetrexed (only in non-squamous histology), and the biological drug anti-epidermal growth factor receptor (EGFR) erlotinib, were approved for clinical use in the second-line treatment of NSCLC patients. In the last few years further new second-line therapies have become available in the clinical practice...
March 1, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28276698/the-role-of-checkpoint-inhibitors-immunotherapy-in-advanced-non-small-cell-lung-cancer-in-the-elderly
#11
Assunta Sgambato, Francesca Casaluce, Cesare Gridelli
Immune checkpoint inhibition is a novel treatment modality that has brought a new hope to patients with advanced NSCLC. Several molecules targeting cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 receptor/programmed death ligand-1 (PD1/PD-L1) pathways are under evaluation in NSCLC and three of them are currently approved: nivolumab and atezolizumab for advanced NSCLC after prior chemotherapy and pembrolizumab for advanced NSCLC expressing PD-L1 ≥ 1% after at least one prior chemotherapy regimen and > 50% as a first-line response...
February 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28276253/safety-profiles-of-non-small-cell-lung-cancer-patients-treated-with-pemetrexed-plus-carboplatin-a-real-world-retrospective-observational-cohort-study
#12
Lei Chen, Belen San Antonio, Yu Yan, Jian Chen, Robert J Goodloe, William J John
OBJECTIVE: Pemetrexed plus carboplatin (PCb) is a frequently used first-line treatment in advanced non-small cell lung cancer (NSCLC). This study examined the characteristics and safety profile of a NSCLC population treated with PCb area under the concentration-time curve 5 (PCb5) or 6 mg/mL•min (PCb6) under real-world conditions. RESEARCH DESIGN AND METHODS: A retrospective, observational, cohort study was conducted, utilizing data from the IMS Oncology US clinic-based, longitudinal, patient-level electronic medical records (EMR), including patients with NSCLC on PCb5 or PCb6 regimens initiated concomitantly on or after the diagnosis of lung cancer during 2004-2014...
March 9, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28274559/a-novel-technique-for-tumor-localization-and-targeted-lymphatic-mapping-in-early-stage-lung-cancer
#13
Krista J Hachey, Christopher S Digesu, Katherine W Armstrong, Denis M Gilmore, Onkar V Khullar, Brian Whang, Hisashi Tsukada, Yolonda L Colson
OBJECTIVE: To investigate safety and feasibility of navigational bronchoscopy (NB)-guided near-infrared (NIR) localization of small, ill-defined lung lesions and sentinel lymph nodes (SLN) for accurate staging in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with known or suspected stage I NSCLC were enrolled in a prospective pilot trial for lesion localization and SLN mapping via NB-guided NIR marking. Successful localization, SLN detection rates, histopathologic status of SLN versus overall nodes, and concordance to initial clinical stage were measured...
February 10, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28274158/heat-shock-protein-antagonists-in-early-stage-clinical-trials-for-nsclc
#14
Lizza E L Hendriks, Anne-Marie C Dingemans
Cancer cells have a higher need of chaperones than normal cells to prevent the toxic effects of intracellular protein misfolding and aggregation. Heat shock proteins (Hsps) belong to these chaperones; they are classified into families according to molecular size. Hsps are upregulated in many cancers and inhibition can inhibit tumor growth by destabilizing proteins necessary for tumor survival. In non-small cell lung cancer (NSCLC), there are three different Hsp antagonist classes that are in (early) clinical trials: Hsp90, Hsp70 and Hsp27 inhibitors...
March 8, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28272463/pd-1-inhibitors-increase-the-incidence-and-risk-of-pneumonitis-in-cancer-patients-in-a-dose-independent-manner-a-meta-analysis
#15
Jiaying Wu, Dongsheng Hong, Xiangnan Zhang, Xiaoyang Lu, Jing Miao
Therapies that targeted PD-1 have shown remarkable rates of durable clinical responses in patients with various tumor types. However, the extent and knowledge of pulmonary toxicities associated with PD-1 blockade, mainly manifested as pneumonitis, remains obscure. In this study, a total of 6360 subjects from 16 phase II/III clinical trials were pooled for meta-analysis to evaluate the overall incidence and risk of PD-1 inhibitors-related pneumonitis in cancer patients. The incidence of pneumonitis during anti-PD-1 immunotherapy was 2...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28268556/association-between-tumor-heterogeneity-and-progression-free-survival-in-non-small-cell-lung-cancer-patients-with-egfr-mutations-undergoing-tyrosine-kinase-inhibitors-therapy
#16
Jiangdian Song, Di Dong, Yanqi Huang, Yali Zang, Zaiyi Liu, Jie Tian
For non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, current staging methods do not accurately predict the risk of disease recurrence after tyrosine kinase inhibitors (TKI) therapy. Developing a noninvasive method to predict whether individual could benefit from TKI therapy has great clinical significance. In this research, a radiomics approach was proposed to determine whether the tumor heterogeneity of NSCLC, which was measured by the texture on computed tomography (CT), could make an independent prediction of progression-free survival (PFS)...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28267397/standard-of-care-in-immunotherapy-trials-challenges-and-considerations
#17
Gareth Rivalland, Andrew M Scott, Thomas John
The success of immunotherapeutics over the past decade has fundamentally altered the therapeutic landscape in melanoma and non-small cell lung (NSCLC) cancer care. Multiple clinical trials have confirmed significant improvements in survival with a variety of immunotherapeutic strategies. The careful and appropriate selection of standard of care (SOC) therapies is key to the successful design and interpretation of these trials. To date immunotherapeutic trials have used best supportive care, matched placebo, chemotherapy, targeted therapy or, more recently, established immunotherapeutics in melanoma clinical trials as SOCs...
March 1, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28261342/nivolumab-as-programmed-death-1-pd-1-inhibitor-for-targeted-immunotherapy-in-tumor
#18
REVIEW
Liting Guo, Haijun Zhang, Baoan Chen
Targeted immunotherapy has become the most promising approach for tumor patients. Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, can reverse immune suppression and release T cell activation. Nivolumab, a fully human immunoglobulin G4 PD-1 immune checkpoint inhibitor antibody, blocks PD-1 and promotes antitumor immunity, and it is effective for treating non-small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC) and other cancers. The present review summarizes the efficacy and current status of clinical trials of nivolumab and that enabled nivolumab to be investigated in patients...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28260402/cost-and-survival-analysis-before-and-after-implementation-of-dana-farber-clinical-pathways-for-patients-with-stage-iv-non-small-cell-lung-cancer
#19
David M Jackman, Yichen Zhang, Carole Dalby, Tom Nguyen, Julia Nagle, Christine A Lydon, Michael S Rabin, Kristen K McNiff, Belen Fraile, Joseph O Jacobson
PURPOSE: Increasing costs and medical complexity are significant challenges in modern oncology. We explored the use of clinical pathways to support clinical decision making and manage resources prospectively across our network. MATERIALS AND METHODS: We created customized lung cancer pathways and partnered with a commercial vendor to provide a Web-based platform for real-time decision support and post-treatment data aggregation. Dana-Farber Cancer Institute (DFCI) Pathways for non-small cell lung cancer (NSCLC) were introduced in January 2014...
March 4, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28259750/long-term-outcomes-of-salvage-stereotactic-ablation-radiotherapy-for-isolated-lung-recurrence-of-non-small-cell-lung-cancer-a-phase-ii-clinical-trial
#20
Bing Sun, Eric D Brooks, Ritsuko Komaki, Zhongxing Liao, Melenda Jeter, Mary McAleer, Peter A Balter, James D Welsh, Michael O'Reilly, Daniel Gomez, Stephen M Hahn, Boris Sepesi, David C Rice, John V Heymach, Joe Y Chang
OBJECTIVES: Our goal was to evaluate stereotactic ablative radiotherapy (SABR) as a salvage option for isolated recurrence of non-small-cell lung cancer (NSCLC) in the lung parenchyma following definitive treatment of stage I-III disease. METHODS: Patients who had histologically confirmed, positron emission tomography (PET) staged, isolated NSCLC recurring locally or metastasis in the lung parenchyma (≤3 cm, suitable for SABR) after previous definitive treatment, were prospectively enrolled in this trial and treated with volumetric, image-guided SABR to 50 Gy in four fractions...
March 1, 2017: Journal of Thoracic Oncology
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