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https://www.readbyqxmd.com/read/27922280/ganetespib-for-small-cell-lung-cancer
#1
Deepa S Subramaniam, Eiran A Warner, Giuseppe Giaccone
Heat shock proteins (Hsps) are part of a complex network of chaperone proteins that are critically involved in the conformational maturation of intracellular proteins and regulate their degradation via the proteasome system Hsps (especially Hsp70 and Hsp90) are upregulated in many cancers and are potentially attractive therapeutic targets. Ganetespib is a potent non-geldanamycin analogue, and avoids the toxicities associated with older analogues due to its small molecular weight, lipophilicity and the absence of the benzoquinone moiety; strong pre-clinical data support its evaluation in lung cancer, especially small cell lung cancer (SCLC)...
December 6, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27920137/oncogenic-met-as-an-effective-therapeutic-target-in-non-small-cell-lung-cancer-resistant-to-egfr-inhibitors-the-rise-of-the-phoenix
#2
Livio Trusolino
Anecdotal reports have shown that concomitant inhibition of EGFR and MET can be clinically effective in patients with non-small cell lung cancer carrying EGFR mutations and MET amplification, but large phase III trials in genetically unselected individuals have failed to confirm the benefit of this combination therapy. A new study corroborates the evidence that lung cancer susceptibility to EGFR and MET blockade is sustained by genetically based activation of both targets and identifies a mutation in MET that confers acquired resistance to standard MET inhibitors hitting the active kinase, yet is vulnerable to other MET-directed compounds with a different binding mode...
December 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27913776/necitumumab-for-the-treatment-of-squamous-cell-non-small-cell-lung-cancer
#3
Jessica K Brinkmeyer, Donald C Moore
Non-small cell lung cancer is the most common form of lung cancer, accounting for about 85% of all cases and is further subdivided into adenocarcinoma, squamous cell, and large cell carcinoma. Necitumumab (Portrazza™, Eli Lilly and Company) is an anti-epidermal growth factor receptor monoclonal antibody approved for the first-line treatment of squamous cell non-small cell lung cancer in combination with cisplatin and gemcitabine. The safety and efficacy of necitumumab has been evaluated in two-phase III clinical trials, one demonstrating a lack of efficacy in non-squamous non-small cell lung cancer and another demonstrating improvement in overall survival and progression-free survival in squamous cell non-small cell lung cancer...
December 2, 2016: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/27910704/the-safety-of-nivolumab-for-the-treatment-of-advanced-non-small-cell-lung-cancer
#4
Giulio Metro, Biagio Ricciuti, Marta Brambilla, Sara Baglivo, Irene Soli, Elisa Minenza, Giulia Costanza Leonardi, Alessandro D'Arpino, Daniela Colabrese, Marco Tazza, Daniela Zicari, Vincenzo Minotti, Rita Chiari
Immune checkpoint blockaders (ICBs) act by unbalancing the immune system, thus favoring the development of an immune-mediated antitumor effect. ICBs targeting the programmed cell death receptor-1 (PD-1) have recently been investigated in a number of advanced tumors, including non-small cell lung cancer (NSCLC). Nivolumab, a fully human IgG4 kappa directed against PD-1, has been the first ICB to be approved for second-line treatment of advanced NSCLC. Areas covered: In this review we focus on the clinical development of nivolumab for the treatment of advanced NSCLC, with an emphasis on its safety profile...
December 2, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27894601/treatment-rationale-and-study-design-for-the-relay-study-a-multicenter-randomized-double-blind-study-of-erlotinib-with-ramucirumab-or-placebo-in-patients-with-epidermal-growth-factor-receptor-mutation-positive-metastatic-non-small-cell-lung-cancer
#5
Edward B Garon, Martin Reck, Luis Paz-Ares, Santiago Ponce, Jesus Corral Jaime, Oscar Juan, Ernest Nadal, Pablo Lee, Rita Dalal, Jingyi Liu, Shuang He, Joseph Treat, Kazuhiko Nakagawa
INTRODUCTION: We present the treatment rationale and study design for the RELAY study (NCT02411448 ). This phase Ib/III study will assess safety, tolerability, and efficacy of the combination of ramucirumab with erlotinib in previously untreated stage IV non-small-cell lung cancer patients with an activating epidermal growth factor receptor (EGFR) mutation. PATIENTS AND METHODS: The study is being conducted in approximately 120 sites in North America, Europe, and Asia and is currently open for enrollment...
June 8, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27893326/randomized-prospective-biomarker-trial-of-ercc1-for-comparing-platinum-and-nonplatinum-therapy-in-advanced-non-small-cell-lung-cancer-ercc1-trial-et
#6
Siow Ming Lee, Mary Falzon, Fiona Blackhall, James Spicer, Marianne Nicolson, Abhro Chaudhuri, Gary Middleton, Samreen Ahmed, Jonathan Hicks, Barbara Crosse, Mark Napier, Julian M Singer, David Ferry, Conrad Lewanski, Martin Forster, Sally-Ann Rolls, Arrigo Capitanio, Robin Rudd, Natasha Iles, Yenting Ngai, Michael Gandy, Rachel Lillywhite, Allan Hackshaw
Purpose Retrospective studies indicate that expression of excision repair cross complementing group 1 (ERCC1) protein is associated with platinum resistance and survival in non-small-cell lung cancer (NSCLC). We conducted the first randomized trial, to our knowledge, to evaluate ERCC1 prospectively and to assess the superiority of nonplatinum therapy over platinum doublet therapy for ERCC1-positive NSCLC as well as noninferiority for ERCC1-negative NSCLC. Patients and Methods This trial had a marker-by-treatment interaction phase III design, with ERCC1 (8F1 antibody) status as a randomization stratification factor...
November 28, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27892773/real-world-data-on-nivolumab-treatment-of-non-small-cell-lung-cancer
#7
O T Brustugun, M Sprauten, Å Helland
BACKGROUND: Checkpoint inhibitors have proven effectiveness in clinical trials for non-small cell lung cancer (NSCLC) patients, but if this is congruent with routine patient care is discussed. We present real-world experience with the PD1-inhibitor nivolumab in NSCLC. PATIENTS AND METHODS: Patients with NSCLC were considered eligible for nivolumab treatment after one or more lines of chemotherapy, and when in reasonable performance status (PS) [Eastern Cooperative Oncology Group (ECOG) < 3]...
November 28, 2016: Acta Oncologica
https://www.readbyqxmd.com/read/27879974/nivolumab-dose-selection-challenges-opportunities-and-lessons-learned-for-cancer-immunotherapy
#8
Shruti Agrawal, Yan Feng, Amit Roy, Georgia Kollia, Brian Lestini
BACKGROUND: Immuno-oncology (I-O) therapies target the host immune system, providing the potential to choose a uniform dose and schedule across tumor types. However, dose selection for I-O agents usually occurs early in clinical development and is typically based on tumor response, which may not fully represent the potential for improved overall survival. Here, we describe an integrated approach which incorporates clinical safety and efficacy data with data obtained from analyses of dose-/exposure-response (D-R/E-R) relationships, used to select a monotherapy dose for nivolumab, a programmed death-1 inhibitor, in clinical studies of different tumor types...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27876603/canadian-phase-iii-randomized-trial-of-stereotactic-body-radiotherapy-versus-conventionally-hypofractionated-radiotherapy-for-stage-i-medically-inoperable-non-small-cell-lung-cancer-rationale-and-protocol-design-for-the-ontario-clinical-oncology-group-ocog
#9
Anand Swaminath, Marcin Wierzbicki, Sameer Parpia, James R Wright, Theodoros K Tsakiridis, Gordon S Okawara, Vijayananda Kundapur, Alexis Bujold, Naseer Ahmed, Khalid Hirmiz, Elizabeth Kurien, Edith Filion, Zsolt Gabos, Sergio Faria, Alexander V Louie, Timothy Owen, Elaine Wai, Kevin Ramchandar, Elisa K Chan, Jim Julian, Kathryn Cline, Timothy J Whelan
We describe a Canadian phase III randomized controlled trial of stereotactic body radiotherapy (SBRT) versus conventionally hypofractionated radiotherapy (CRT) for the treatment of stage I medically inoperable non-small-cell lung cancer (OCOG-LUSTRE Trial). Eligible patients are randomized in a 2:1 fashion to either SBRT (48 Gy in 4 fractions for peripherally located lesions; 60 Gy in 8 fractions for centrally located lesions) or CRT (60 Gy in 15 fractions). The primary outcome of the study is 3-year local control, which we hypothesize will improve from 75% with CRT to 87...
October 3, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27855622/the-role-of-the-antiangiogenetic-ramucirumab-in-the-treatment-of-advanced-non-small-cell-lung-cancer
#10
Paolo Maione, Assunta Sgambato, Francesca Casaluce, Paola Claudia Sacco, Giuseppe Santabarbara, Antonio Rossi, Cesare Gridelli
Angiogenesis is one of the most important phenomena sustaining tumor development and metastatization, including for non small cell lung cancer (NSCLC). A dominant role in angiogenesis is played by the vascular endothelial growth factor (VEGF) and its signalling pathway. Ramucirumab, is a fully human immunoglobulin G1 monoclonal antibody that binds to the extracellular domain of the VEGF receptor-2 (VEGFR-2) with high specificity and affinity blocking the interaction of VEGFR-2 and VEGF ligands, thus inhibiting their signaling pathways and the consequential endothelial proliferation and migration...
November 18, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27846725/-non-small-cell-lung-cancer-from-immunobiology-to-immunotherapy
#11
O Bílek, L Bohovicová, R Demlová, A Poprach, R Lakomý, L Zdražilová-Dubská
BACKGROUND: The treatment of early or locally advanced stages of non-small cell lung cancer (NSCLC) is based on surgical resection or radiotherapy. Metastatic disease is always incurable, treatment is palliative, systemic based on chemotherapy or target therapy. NSCLC is the most common cause of cancer-related death worldwide, and new therapeutic approaches are needed. Based on the emerging data on the role of immune system in shaping of tumor outbreak and outcome, immunotherapy is currently in the center of interest of cancer research and therapy of solid cancers including NSCLC...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27830967/the-european-society-for-medical-oncology-magnitude-of-clinical-benefit-scale-esmo-mcbs-applied-to-pivotal-phase-iii-randomized-controlled-trials-of-tyrosine-kinase-inhibitors-in-first-line-for-advanced-non-small-cell-lung-cancer-with-activating-epidermal-growth
#12
Jacopo Giuliani, Andrea Remo, Andrea Bonetti
To examine the magnitude of the clinical benefit from first-line tyrosine kinase inhibitors (TKIs) advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR)-mutations. Areas covered: The present evaluation was restricted to pivotal phase III RCTs in first-line for advanced NSCLC with activating EGFR-mutations. We have subsequently applied the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) to the above pivotal phase III RCTs, to derive a relative ranking of the magnitude of clinically meaningful benefit...
November 21, 2016: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/27788387/postoperative-radiotherapy-for-lung-cancer-is-it-worth-the-controversy
#13
REVIEW
Charlotte Billiet, Stéphanie Peeters, Herbert Decaluwé, Johan Vansteenkiste, Jeroen Mebis, Dirk De Ruysscher
INTRODUCTION: The role of postoperative radiation therapy (PORT) in patients with completely resected non-small cell lung cancer (NSCLC) with pathologically involved mediastinal lymph nodes (N2) remains unclear. Despite a reduction of local recurrence (LR), its effect on overall survival (OS) remains unproven. Therefore we conducted a review of the current literature. METHODS: To investigate the benefit and safety of modern PORT, we identified published phase III trials for PORT...
December 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27786238/the-efficacy-and-risk-profile-of-c-met-inhibitors-in-non-small-cell-lung-cancer-a-meta-analysis
#14
Sa Ye, Jiuke Li, Ke Hao, Jianping Yan, Hongbin Zhou
c-MET inhibitors are considered as a kind of novel drugs in non-small cell lung cancer (NSCLC) treatment. However, the results of different clinical studies involving c-MET inhibitors were not consistent. In this report, we performed Meta-analysis to investigate the beneficial and harmful effects of these drugs from 9 studies including 1611 patients in target drug groups and 1605 patients in control groups. As a result, patients in target drugs group had longer progression free survival (PFS) (HR 0.80, 95% CI 0...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27780368/alectinib-for-treatment-of-alk-positive-non-small-cell-lung-cancer
#15
Virginie Avrillon, Maurice Pérol
Alectinib is a highly selective second-generation ALK inhibitor that is active against most crizotinib ALK resistance mutations, with a good penetration in CNS and a good safety profile. Thanks to the positive results of Phase II trials, alectinib was approved in Japan and by the US FDA for ALK-positive non-small-cell lung cancer (NSCLC) patients pretreated with crizotinib. Recently, the Phase III J-ALEX study demonstrated superiority of alectinib over crizotinib in crizotinib naive ALK-positive NSCLC, with an impressive improvement of progression-free survival...
October 26, 2016: Future Oncology
https://www.readbyqxmd.com/read/27771969/vinflunine-for-the-treatment-of-non-small-cell-lung-cancer
#16
C Genova, A Alama, S Coco, E Rijavec, M G Dal Bello, I Vanni, F Biello, G Barletta, G Rossi, F Grossi
Vinflunine belongs to the class of vinca alkaloids and acts by disrupting the microtubule dynamics during cell cycle; this agent is currently available for previously treated advanced transitional cell carcinoma in Europe. The aim of this invited review is to evaluate the potential role of vinflunine for the treatment of non-small cell lung cancer (NSCLC). Areas covered: The potential role of vinflunine in NSCLC is discussed on the basis of the available data, including full papers and meeting abstracts. Relevant preclinical studies describing the pharmacological properties of vinflunine are also included...
November 1, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27764781/a-phase-ii-open-label-multicenter-study-of-gefitinib-in-combination-with-irradiation-followed-by-chemotherapy-in-patients-with-inoperable-stage-iii-non-small-cell-lung-cancer
#17
Antonin Levy, Etienne Bardet, Benjamin Lacas, Jean-Pierre Pignon, Julien Adam, Ludovic Lacroix, Xavier Artignan, Pierre Verrelle, Cécile Le Péchoux
BACKGROUND: Gefitinib is an oral EGFR tyrosine kinase inhibitors which may act as a radiosensitizer. PATIENTS AND METHODS: This phase II study evaluated the efficacy of gefitinib 250 mg once daily in combination with thoracic radiotherapy (66 Gy in 6.5 weeks, 2 Gy/day, 5 fractions/week) followed by consolidation chemotherapy (IV cisplatin and vinorelbine) as first line treatment in a population of unselected stage IIIB NSCLC patients according to EGFR mutation status...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27760599/-progress-in-immunotherapy-for-squamous-non-small-cell-lung-cancer
#18
Shouzheng Wang, Junling Li
In recent years, squamous non-small cell lung cancer (NSCLC) didn't progress much in chemotherapy or target therapy. However, immunotherapy has made breakthroughs in treating squamous NSCLC. Immunotherapy includes two main broad classes of immune checkpoint inhibitors and therapeutic vaccines. Immune checkpoint inhibitors, including anti cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and anti programmed death receptor 1 (PD-1) antibodies, have been tested in the phase II/III clinical trials and have demonstrated promising outcomes...
October 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/27754528/-clinical-trials-and-licensing-of-monoclonal-antibodies-and-biological-medicines-for-cancer-treatment-in-brazil
#19
Cecilia Ferreira da Silva, Miriam Ventura da Silva, Claudia Garcia Serpa Osorio-de-Castro
Objective To analyze the pathway of clinical trials of monoclonal antibodies and biological medicines for cancer treatment involving Brazilian institutions from 2003 to 2012. Method This retrospective, descriptive study was based on review of two clinical trial registries, ClinicalTrials.gov and the Brazilian registry ReBEC. Phase II or III studies with participation from Brazilian institutions listed in at least one of the registries were included. Following selection of the trials, the pathway of monoclonal antibodies and biological medicines was investigated from the research stage until licensing by the Brazilian Agency for Sanitary Surveillance (Anvisa), Food and Drug Administration (FDA), and European Medicines Agency (EMA)...
March 2016: Revista Panamericana de Salud Pública, Pan American Journal of Public Health
https://www.readbyqxmd.com/read/27745983/stereotactic-body-radiation-therapy-boost-after-concurrent-chemoradiation-for-locally-advanced-non-small-cell-lung-cancer-a-phase-1-dose-escalation-study
#20
Jaroslaw T Hepel, Kara Lynne Leonard, Howard Safran, Thomas Ng, Angela Taber, Humera Khurshid, Ariel Birnbaum, David E Wazer, Thomas DiPetrillo
PURPOSE: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). METHODS AND MATERIALS: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively)...
December 1, 2016: International Journal of Radiation Oncology, Biology, Physics
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