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https://www.readbyqxmd.com/read/28929083/emerging-therapies-for-stage-iii-non-small-cell-lung-cancer-stereotactic-body-radiation-therapy-and-immunotherapy
#1
REVIEW
Sameera S Kumar, Kristin A Higgins, Ronald C McGarry
The current standard of care for locally advanced non-small cell lung cancer (NSCLC) includes radiation, chemotherapy, and surgery in certain individualized cases. In unresectable NSCLC, chemoradiation has been the standard of care for the past three decades. Local and distant failure remains high in this group of patients, so dose escalation has been studied in both single institution and national clinical trials. Though initial studies showed a benefit to dose escalation, phase III studies examining dose escalation using standard fractionation or hyperfractionation have failed to show a benefit...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28923104/phase-1-study-of-intravenous-administration-of-the-chimeric-adenovirus-enadenotucirev-in-patients-undergoing-primary-tumor-resection
#2
Rocio Garcia-Carbonero, Ramon Salazar, Ignacio Duran, Ignacio Osman-Garcia, Luis Paz-Ares, Juan M Bozada, Valentina Boni, Christine Blanc, Len Seymour, John Beadle, Simon Alvis, Brian Champion, Emiliano Calvo, Kerry Fisher
BACKGROUND: Enadenotucirev (formerly ColoAd1) is a tumor-selective chimeric adenovirus with demonstrated preclinical activity. This phase 1 Mechanism of Action study assessed intravenous (IV) delivery of enadenotucirev in patients with resectable colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), urothelial cell cancer (UCC), and renal cell cancer (RCC) with a comparator intratumoral (IT) dosed CRC patient cohort. METHODS: Seventeen patients scheduled for primary tumor resection were enrolled...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28923084/viral-based-vaccine-tg4010-induces-broadening-of-specific-immune-response-and-improves-outcome-in-advanced-nsclc
#3
Caroline Tosch, Bérangère Bastien, Luc Barraud, Benoit Grellier, Virginie Nourtier, Murielle Gantzer, Jean Marc Limacher, Eric Quemeneur, Kaïdre Bendjama, Xavier Préville
BACKGROUND: Advanced non-small cell lung cancer patients receiving TG4010, a therapeutic viral vaccine encoding human Mucin 1 and interleukin-2 in addition to standard chemotherapy, displayed longer overall survival in comparison to that of patients treated with standard chemotherapy alone. Our study intended to establish the association between overall survival and vaccine-induced T cell responses against tumor associated antigens (TAA) targeted by the vaccine. METHOD: The TIME trial was a placebo-controlled, randomized phase II study aimed at assessing efficacy of TG4010 with chemotherapy in NSCLC...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28922791/targeting-hypoxia-to-improve-non-small-cell-lung-cancer-outcome
#4
Ahmed Salem, Marie-Claude Asselin, Bart Reymen, Alan Jackson, Philippe Lambin, Catharine M L West, James P B O'Connor, Corinne Faivre-Finn
Oxygen deprivation (hypoxia) in non-small cell lung cancer (NSCLC) is an important factor in treatment resistance and poor survival. Hypoxia is an attractive therapeutic target, particularly in the context of radiotherapy, which is delivered to more than half of NSCLC patients. However, NSCLC hypoxia-targeted therapy trials have not yet translated into patient benefit. Recently, early termination of promising evofosfamide and tarloxotinib bromide studies due to futility highlighted the need for a paradigm shift in our approach to avoid disappointments in future trials...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28919011/dabrafenib-plus-trametinib-in-patients-with-previously-untreated-braf-v600e-mutant-metastatic-non-small-cell-lung-cancer-an-open-label-phase-2-trial
#5
David Planchard, Egbert F Smit, Harry J M Groen, Julien Mazieres, Benjamin Besse, Åslaug Helland, Vanessa Giannone, Anthony M D'Amelio, Pingkuan Zhang, Bijoyesh Mookerjee, Bruce E Johnson
BACKGROUND: BRAF(V600E) mutation occurs in 1-2% of lung adenocarcinomas and acts as an oncogenic driver. Dabrafenib, alone or combined with trametinib, has shown substantial antitumour activity in patients with previously treated BRAF(V600E)-mutant metastatic non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of dabrafenib plus trametinib treatment in previously untreated patients with BRAF(V600E)-mutant metastatic NSCLC. METHODS: In this phase 2, sequentially enrolled, multicohort, multicentre, non-randomised, open-label study, adults (≥18 years of age) with previously untreated metastatic BRAF(V600E)-mutant NSCLC were enrolled into cohort C from 19 centres in eight countries within North America, Europe, and Asia...
September 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28917258/stereotactic-body-radiotherapy-for-early-stage-lung-cancer-historical-developments-and-future-strategies
#6
Kevin L M Chua, Iris Sin, Kam W Fong, Melvin L K Chua, Hiroshi Onishi
The application of radiosurgery dose escalation extra-cranially in a moving target, surrounded by critical normal tissue, presents unique dosimetric and clinical challenges. Building on a strong foundation of robust technological advancements and well-planned clinical studies, lung stereotactic body radiotherapy (SBRT) has firmly established its place in the management of early stage non-small cell lung cancer (NSCLC). Nevertheless, favourable outcomes and long-term survival still evade a substantial proportion of patients, especially for central and larger peripheral lung tumours...
September 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28917254/stereotactic-radiotherapy-in-oligometastatic-cancer
#7
Thomas A C Kennedy, Mark T Corkum, Alexander V Louie
Oligometastatic cancer describes a disease state somewhere between localized and metastatic cancer. Proposed definitions of oligometastatic disease have typically used a cut-off of five or fewer sites of disease. Treatment of oligometastatic disease should have the goal of long-term local control, and in selected cases, disease remission. While several retrospective cohorts argue for surgical excision of limited metastases (metastasectomy) as the preferred treatment option for several clinical indications, limited randomized data exists for treating oligometastases...
September 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28916617/nivolumab-exposure-response-analyses-of-efficacy-and-safety-in-previously-treated-squamous-or-nonsquamous-non-small-cell-lung-cancer
#8
Yan Feng, Xiaoning Wang, Gaurav Bajaj, Shruti Agrawal, Akintunde Bello, Brian Lestini, Friedrich Graf Finckenstein, Jong-Soon Park, Amit Roy
Purpose: Nivolumab is a fully human IgG4 monoclonal antiprogrammed death-1 antibody with demonstrated efficacy, including durable responses and prolonged survival, in patients with previously treated, advanced non-small cell lung cancer (NSCLC). Exposure-response (E-R) analyses for efficacy and safety were conducted to inform the benefit-risk assessment of nivolumab in this patient population.Experimental Design: The analyses used clinical trial data from patients with squamous (n = 293) or nonsquamous (n = 354) NSCLC from four clinical trials who received nivolumab doses of 1 to 10 mg/kg every 2 weeks...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28916198/treatment-outcome-and-quality-of-life-of-1239-patients-with-advanced-non-small-cell-lung-cancer-final-results-from-the-prospective-german-tlk-cohort-study
#9
Ulla von Verschuer, Roland Schnell, Hans Werner Tessen, Jochen Eggert, Adrian Binninger, Lisa Spring, Martina Jänicke, Norbert Marschner
OBJECTIVES: Real-life data on advanced non-small cell lung cancer (NSCLC) are centrally important to complement the results from clinical trials and to improve the standard of care. We present data on the choice of systemic first- and second-line treatment, number of treatment lines, survival and longitudinal data on health-related quality of life (HRQOL) of patients treated by medical oncologists in Germany. MATERIALS AND METHODS: 1239 patients with advanced NSCLC were recruited at start of first-line therapy into the prospective German clinical cohort study TLK (Tumour Registry Lung Cancer) by 107 sites between February 2010 and December 2013 and followed-up until January 2016...
August 22, 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28915708/targeting-metabolism-and-amp-activated-kinase-with-metformin-to-sensitize-non-small-cell-lung-cancer-nsclc-to-cytotoxic-therapy-translational-biology-and-rationale-for-current-clinical-trials
#10
REVIEW
Michael Troncone, Stephanie M Cargnelli, Linda A Villani, Naghmeh Isfahanian, Lindsay A Broadfield, Laura Zychla, Jim Wright, Gregory Pond, Gregory R Steinberg, Theodoros Tsakiridis
Lung cancer is the most fatal malignancy worldwide, in part, due to high resistance to cytotoxic therapy. There is need for effective chemo-radio-sensitizers in lung cancer. In recent years, we began to understand the modulation of metabolism in cancer and its importance in tumor progression and survival after cytotoxic therapy. The activity of biosynthetic pathways, driven by the Growth Factor Receptor/Ras/PI3k/Akt/mTOR pathway, is balanced by the energy stress sensor pathway of LKB1/AMPK/p53. AMPK responds both to metabolic and genotoxic stress...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915678/meta-analysis-of-the-incidence-and-risks-of-interstitial-lung-disease-and-qtc-prolongation-in-non-small-cell-lung-cancer-patients-treated-with-alk-inhibitors
#11
Liping Lin, Juanjuan Zhao, Ning Kong, Yan He, Jiazhu Hu, Fuxi Huang, Jianjun Han, Xiaolong Cao
BACKGROUND: To conduct a systematic review and meta-analysis to assess the overall incidence and risk of interstitial lung disease (ILD) and QTc prolongation associated with anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (-TKIs) in non-small-cell lung cancer (NSCLC) patients. RESULTS: A total of 1,770 patients from 8 clinical trials were included. The incidences of high-grade ILD and QTc prolongation was 2.5% (95% CI 1.7-3.6%), and 2.8% (95% CI 1.8-4...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28905108/a-randomized-phase-ii-trial-of-erlotinib-vs-s-1-as-a-third-or-fourth-line-therapy-for-patients-with-wild-type-egfr-non-small-cell-lung-cancer-hot1002
#12
Yasuyuki Ikezawa, Hajime Asahina, Satoshi Oizumi, Masahiro Watanabe, Kei Takamura, Yasutaka Kawai, Noriyuki Yamada, Toshiyuki Harada, Ichiro Kinoshita, Yuka Fujita, Eisaku Miyauchi, Takahiro Ogi, Toraji Amano, Megumi Furuta, Jun Sakakibara-Konishi, Hiroshi Nishihara, Hirotoshi Dosaka-Akita, Hiroshi Isobe, Masaharu Nishimura
PURPOSE: A high proportion of patients with wild-type EGFR non-small cell lung cancer (NSCLC) receive third-line therapy and beyond, with no prospective randomized trials addressing the issue. This study aimed to select the most suitable regimen as a third- or fourth-line therapy for wild-type EGFR NSCLC. METHODS: This multicenter, randomized phase II study in Japan included patients with recurrent or advanced NSCLC with wild-type or unknown EGFR, who progressed after two or three previous chemotherapies...
September 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28904891/clinical-utility-of-circulating-tumor-cells-in-patients-with-non-small-cell-lung-cancer
#13
REVIEW
Marianna Gallo, Antonella De Luca, Monica Rosaria Maiello, Amelia D'Alessio, Claudia Esposito, Nicoletta Chicchinelli, Laura Forgione, Maria Carmela Piccirillo, Gaetano Rocco, Alessandro Morabito, Gerardo Botti, Nicola Normanno
Several different studies have addressed the role of the circulating tumor cells (CTC) in non-small-cell lung cancer (NSCLC). In particular, the potential of CTC analysis in the early diagnosis of NSCLC and in the prediction of the outcome of patients with early and advanced NSCLC have been explored. A major limit of these studies is that they used different techniques for CTC isolation and enumeration, they employed different thresholds to discriminate between high- and low-risk patients, and they enrolled heterogeneous and often small cohort of patients...
August 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28900765/serum-25-hydroxyvitamin-d-concentrations-and-lung-cancer-risk-in-never-smoking-postmenopausal-women
#14
Ting-Yuan David Cheng, Xiaoling Song, Shirley A A Beresford, Gloria Y F Ho, Karen C Johnson, Mridul Datta, Rowan T Chlebowski, Jean Wactawski-Wende, Lihong Qi, Marian L Neuhouser
PURPOSE: Vitamin D has been implicated in lowering lung cancer risk, but serological data on the association among never-smoking women are limited. We report results examining the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with lung cancer risk among female never smokers. We also examined whether the association was modified by vitamin D supplementation and serum vitamin A concentrations. METHODS: In the Women's Health Initiative, including the calcium/vitamin D (CaD) Trial, we selected 298 incident cases [191 non-small cell lung cancer (NSCLC) including 170 adenocarcinoma] and 298 matched controls of never smokers...
September 12, 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28900290/alteration-of-pd-l1-expression-and-its-prognostic-impact-after-concurrent-chemoradiation-therapy-in-non-small-cell-lung-cancer-patients
#15
Daichi Fujimoto, Keiichiro Uehara, Yuki Sato, Ichiro Sakanoue, Munehiro Ito, Shunsuke Teraoka, Kazuma Nagata, Atsushi Nakagawa, Yasuhiro Kosaka, Kojiro Otsuka, Yukihiro Imai, Hiroshi Hamakawa, Yutaka Takahashi, Masaki Kokubo, Keisuke Tomii
Concurrent chemoradiation therapy (CCRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD-1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CCRT on programmed cell death ligand-1 (PD-L1) expression on tumor cells is unknown. In this study, we analysed paired NSCLC specimens that had been obtained pre- and post-CCRT. PD-L1 expression on tumor cells was studied by immunohistochemistry...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28891712/molecular-and-clinical-features-of-second-generation-anaplastic-lymphoma-kinase-inhibitors-ceritinib
#16
Tommaso De Pas, Laura Pala, Chiara Catania, Fabio Conforti
The discovery of ALK rearrangement in non-small-cell lung cancer (NSCLC) triggered rapid clinical development of a family of specific drugs targeting this alteration, called ALK inhibitors. Despite high rate of responses, the vast majority of patients treated with first-generation ALK inhibitor crizotinib will ultimately develop disease progression. The second-generation ALK inhibitor, ceritinib, is an oral, small-molecule that inhibits the ALK kinase activity with a potency 20-fold greater than crizotinib, being able to tackle some of the principal mechanisms of resistance to crizotinib...
September 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/28889085/immunosenescence-and-immunecheckpoint-inhibitors-in-non-small-cell-lung-cancer-patients-does-age-really-matter
#17
REVIEW
Roberto Ferrara, Laura Mezquita, Edouard Auclin, Nathalie Chaput, Benjamin Besse
Immunotherapy has dramatically changed the therapeutic scenario in non-small cell lung cancer (NSCLC), extending overall survival, with a favorable safety profile. However, there is still a gap of knowledge about the efficacy of immune checkpoint inhibitors (ICIs) in elderly patients. Data from randomized clinical trials testing ICIs are conflicting and often lack adequate statistical power. Although two large meta-analyses suggested an absence of a significant survival benefit in patients older than 75years, expanded access programs and retrospective cohort studies of ICIs in the real-life setting, showed comparable survival outcomes and safety profiles between older and younger patients...
August 24, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28888101/what-s-new-in-sclc-a-review
#18
REVIEW
Bryan Oronsky, Tony R Reid, Arnold Oronsky, Corey A Carter
A few years ago the answer to the question in the title of this review would have been, "unfortunately not much" or even "nothing", likely eliciting knowing nods of agreement from oncologists. For the last 3 decades, SCLC has been notorious for its lack of progress, as drug after drug, over 60 of them, in fact, including inhibitors of VEGF, IGFR, mTOR, EGFR and HGF has failed and fallen by the wayside due to little or no impact on PFS or OS, while SCLC's cousin, NSCLC, has notched success after success with a spate of targeted treatment and immunotherapy regulatory approvals...
September 6, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28883282/development-of-immune-checkpoint-inhibitors
#19
Shigehisa Kitano
Immune checkpoint inhibitors are the most striking innovation in the clinical development of immunotherapy. Monoclonal antibodies (mAbs) restore and augment the antitumor immune activities of cytotoxic T cells by mainly blocking immune checkpoint molecules on T cells or their ligands on antigen-presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of mAb in various cancers. The A first-in-class approved immune checkpoint inhibitor is ipilimumab, which is a fully humanized mAb that blocks the immunosuppressive signal by cytotoxic T-lymphocyte antigen 4...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28880737/cost-effectiveness-of-osimertinib-in-the-uk-for-advanced-egfr-t790m-non-small-cell-lung-cancer
#20
Evelina Bertranou, Carolyn Bodnar, Viktor Dansk, Alastair Greystoke, Samuel Large, Matthew Dyer
AIM: This study presents the cost-utility analysis that was developed to inform the NICE health technology assessment of osimertinib versus platinum-based doublet chemotherapy (PDC) in patients with EGFR-T790M mutation-positive non-small cell lung cancer (NSCLC) who have progressed on epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. METHODS AND MATERIALS: A partitioned survival model with three health states (progression-free, progressed disease, and death) from a UK payer perspective and over lifetime (15 years) was developed...
September 7, 2017: Journal of Medical Economics
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