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Non small cell lung cancer phase iii

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https://www.readbyqxmd.com/read/28727865/proton-beam-radiotherapy-and-concurrent-chemotherapy-for-unresectable-stage-iii-non-small-cell-lung-cancer-final-results-of-a-phase-2-study
#1
Joe Y Chang, Vivek Verma, Ming Li, Wencheng Zhang, Ritsuko Komaki, Charles Lu, Pamela K Allen, Zhongxing Liao, James Welsh, Steven H Lin, Daniel Gomez, Melenda Jeter, Michael O'Reilly, Ronald X Zhu, Xiaodong Zhang, Heng Li, Radhe Mohan, John V Heymach, Ara A Vaporciyan, Stephen Hahn, James D Cox
Importance: Proton beam radiotherapy (PBT) has the potential to reduce toxic effects in the definitive management of locally advanced non-small-cell lung cancer (NSCLC), but long-term prospective data are lacking. Objective: To report the final (5-year) results of a prospective study evaluating concurrent chemotherapy and high-dose PBT to treat unresectable stage III NSCLC. Design, Setting, and Participants: In this open-label, single-group assignment study, with median follow-up of 27...
July 20, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28709816/-current-knowledge-on-perioperative-treatments-of-non-small-cell-lung-carcinomas
#2
REVIEW
S Brosseau, C Naltet, M Nguenang, V Gounant, P Mordant, B Milleron, Y Castier, G Zalcman
Surgery is still the main treatment in early-stage of non-small cell lung cancer with 5-year survival of stage IA patients exceeding 80%, but 5-year survival of stage II patients rapidly decreasing with tumor size, N status, and visceral pleura invasion. The major metastatic risk in such patients has supported clinical research assessing systemic or loco-regional perioperative treatments. Modern phase 3 trials clearly validated adjuvant or neo-adjuvant platinum-based chemotherapy in resected stage I-III patients as a standard treatment of which value has been reassessed several independent meta-analyses, showing a 5% benefit in 5y-survival, and a decrease of the relative risk for death around from 12 to 25%...
July 11, 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28705024/medi-4736-durvalumab-in-non-small-cell-lung-cancer
#3
Arnaud Jeanson, Fabrice Barlesi
Immune checkpoint inhibitors (ICI) are now a therapeutic option for advanced non-small cell lung cancer (NSCLC) patients. ICI, such as the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have already been marketed for the treatment of pretreated patients with advanced NSCLC. Other notable PD-L1 inhibitors under development include avelumab and durvalumab. Areas covered: This article reviews literature on durvalumab development, from the preclinical data to the results of phase III clinical trials, whether published or presented at international scientific conferences...
July 13, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28702806/efficacy-and-safety-of-nintedanib-plus-docetaxel-in-patients-with-advanced-lung-adenocarcinoma-complementary-and-exploratory-analyses-of-the-phase-iii-lume-lung-1-study
#4
Maya Gottfried, Jaafar Bennouna, Igor Bondarenko, Jean-Yves Douillard, David F Heigener, Maciej Krzakowski, Anders Mellemgaard, Silvia Novello, Sergei Orlov, Yvonne Summers, Joachim von Pawel, Julia Stöhr, Rolf Kaiser, Martin Reck
BACKGROUND: Nintedanib is a triple angiokinase inhibitor approved with docetaxel for adenocarcinoma non-small cell lung cancer after first-line chemotherapy (FLT). In the phase III LUME-Lung 1 study, overall survival (OS) was significantly longer with nintedanib/docetaxel than with placebo/docetaxel in all adenocarcinoma patients and those with time from start of FLT (TSFLT) <9 months. OBJECTIVE: This study sought to extend analyses from the LUME-Lung 1 study, specifically for adenocarcinoma patients, to explore the impact of clinically relevant characteristics on outcomes such as time to progression after FLT...
July 12, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28701030/crizotinib-versus-chemotherapy-in-asian-patients-with-advanced-alk-positive-non-small-cell-lung-cancer
#5
Makoto Nishio, Dong-Wan Kim, Yi-Long Wu, Kazuhiko Nakagawa, Benjamin J Solomon, Alice T Shaw, Satoshi Hashigaki, Emiko Ohki, Tiziana Usari, Jolanda Paolini, Anna Polli, Keith D Wilner, Tony Mok
Purpose: Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). We report the safety and efficacy of crizotinib in Asian subpopulations of two global phase III trials. Materials and Methods: This analysis evaluated previously treated and untreated patients in two randomized, open-label phase III trials of crizotinib versus chemotherapy in ALK-positive advanced NSCLC in second-line (PROFILE 1007) and first-line settings (PROFILE 1014)...
July 6, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28675058/selumetinib-for-the-treatment-of-non-small-cell-lung-cancer
#6
Francesca Casaluce, Assunta Sgambato, Paolo Maione, Paola Claudia Sacco, Giuseppe Santabarbara, Cesare Gridelli
KRAS is the most frequently mutated oncogene in NSCLC, occurring in around a third of patients. However, this largest genomically defined subgroup of lung cancer patients seem to remain "undruggable", with any effective targeted therapy approved at the moment. The prognostic and predictive power and thus the clinical utility of KRAS oncogenic mutations in lung cancer are highly debated issues, not supportive of KRAS testing in clinical practice of NSCLC therapy. Areas covered: A phase II trial in KRAS-mutant NSCLC had shown significant improvements in PFS and ORR in patients treated with selumetinib plus docetaxel compared to docetaxel alone...
July 4, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28668204/randomized-phase-iii-study-of-cisplatin-with-pemetrexed-and-cisplatin-with-vinorelbine-for-completely-resected-nonsquamous-non-small-cell-lung-cancer-the-jipang-study-protocol
#7
Nobuyuki Yamamoto, Hirotsugu Kenmotsu, Takeharu Yamanaka, Shinichiro Nakamura, Masahiro Tsuboi
This trial report describes the background and design for the Japan Intergroup Trial of Pemetrexed Adjuvant Chemotherapy for Completely Resected Nonsquamous Non-Small-Cell Lung Cancer (JIPANG) study (University Hospital Medical Information Network database: UMIN000006737). Various randomized trials have shown the efficacy of postoperative adjuvant chemotherapy regimens that include cisplatin for resected non-small-cell lung cancer (NSCLC), but the optimal regimen is not known. The JIPANG study is a randomized study comparing cisplatin (75 mg/m(2), day 1) and pemetrexed (500 mg/m(2), day 1) with cisplatin (80 mg/m(2), day 1) and vinorelbine (25 mg/m(2), days 1 and 8) for nonsquamous NSCLC as postoperative adjuvant chemotherapy...
June 8, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28643244/durvalumab-first-global-approval
#8
Yahiya Y Syed
Intravenous durvalumab (Imfinzi™; AstraZeneca) is a fully human monoclonal antibody that blocks programmed cell death ligand-1 binding to its receptors (PD-1 and CD80), resulting in enhanced T-cell responses against cancer cells. The US FDA has granted durvalumab accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy...
June 22, 2017: Drugs
https://www.readbyqxmd.com/read/28641702/-prospect-and-current-situation-of-immune-checkpoint-inhibitors-%C3%A2-in-first-line-treatment-in-advanced-non-small-cell-lung-cancer-patients
#9
REVIEW
Haiyang Wang, Xiaoqing Yu, Yun Fan
With the breakthroughs achieved of programmed death-1 (PD-1)/PD-L1 inhibitors monotherapy as first-line and second-line treatment in advanced non-small cell lung cancer (NSCLC), the treatment strategy is gradually evolving and optimizing. Immune combination therapy expands the benefit population and improves the curative effect. A series of randomized phase III trials are ongoing. In this review, we discuss the prospect and current situation of immune checkpoint inhibitors in first-line treatment in advanced NSCLC patients...
June 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28624922/targeting-the-pd-1-pd-l1-immune-checkpoint-in-egfr-mutated-or-alk-translocated-non-small-cell-lung-cancer
#10
Olivier Bylicki, Nicolas Paleiron, Jacques Margery, Florian Guisier, Alain Vergnenegre, Gilles Robinet, Jean-Bernard Auliac, Radj Gervais, Christos Chouaid
Immune checkpoint inhibitors, notably antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), have modified the management of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Several PD-1/PD-L1 inhibitors have been approved by health authorities for this indication and others are in clinical development. However, only a subset of patients truly benefits from these agents. For patients with mutated EGFR or translocated ALK NSCLC, for whom an immune checkpoint inhibitor can be prescribed after progression on tyrosine kinase inhibitors and chemotherapy, information is scarce and sometimes contradictory...
June 18, 2017: Targeted Oncology
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
#11
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/28611199/u-s-food-and-drug-administration-approval-summary-atezolizumab-for-metastatic-non-small-cell-lung-cancer
#12
Chana Weinstock, Sean Khozin, Daniel Suzman, Lijun Zhang, Shenghui Tang, Sakar Wahby, Kirsten B Goldberg, Geoffrey Kim, Richard Pazdur
On October 18 2016, the U.S. Food and Drug Administration approved atezolizumab (TECENTRIQ®, Genentech Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR). Median OS in OAK, a phase III trial, was 13.8 months (95% confidence interval [CI] 11...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28600466/alectinib-superior-to-crizotinib-for-alk-nsclc
#13
(no author information available yet)
Findings from the global phase III ALEX trial unequivocally show that alectinib is superior to crizotinib as first-line therapy for ALK+ non-small cell lung cancer. Alectinib more than doubled progression-free survival, significantly reduced the incidence of brain and CNS metastases, and should be considered the new standard of care.
June 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28570742/effect-of-midtreatment-pet-ct-adapted-radiation-therapy-with-concurrent-chemotherapy-in-patients-with-locally-advanced-non-small-cell-lung-cancer-a-phase-2-clinical-trial
#14
Feng-Ming Kong, Randall K Ten Haken, Matthew Schipper, Kirk A Frey, James Hayman, Milton Gross, Nithya Ramnath, Khaled A Hassan, Martha Matuszak, Timothy Ritter, Nan Bi, Weili Wang, Mark Orringer, Kemp B Cease, Theodore S Lawrence, Gregory P Kalemkerian
Importance: Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18F-fludeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival...
June 1, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28566436/reactivation-of-the-p90rsk-cdc25c-pathway-leads-to-bypass-of-the-ganetespib-induced-g2-m-arrest-and-mediates-acquired-resistance-to-ganetespib-in-kras-mutant-nsclc
#15
Suman Chatterjee, Eric H-B Huang, Ian Christie, Timothy F Burns
A subset of non-small cell lung cancers (NSCLC) are dependent upon oncogenic driver mutations including the most frequently observed driver mutant KRAS which is associated with a poor prognosis.   As direct RAS targeting in the clinic has been unsuccessful to date, use of Heat shock protein 90 (Hsp90) inhibitors appeared to be a promising therapy for KRAS mutant NSCLC, however limited clinical efficacy was observed due to rapid resistance. Furthermore, the combination of the Hsp90 inhibitor (Hsp90i), ganetespib and docetaxel was tested in a phase III clinical trial and failed to demonstrate benefit...
May 31, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28560182/epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-in-treatment-of-metastatic-non-small-cell-lung-cancer-with-a-focus-on-afatinib
#16
REVIEW
Sami Morin-Ben Abdallah, Vera Hirsh
Somatic epidermal growth factor receptor (EGFR) mutations are present in around 50% of Asian patients and in 10-15% of Caucasian patients with metastatic non-small cell lung cancer (NSCLC) of adenocarcinoma histology. The first-generation EGFR-tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib have demonstrated improved progression-free survival (PFS) and response rates but not overall survival (OS) benefit in randomized phase III trials when compared with platinum-doublet chemotherapy. All patients treated with EGFR-TKIs will eventually develop acquired resistance to these agents...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28546756/new-developments-in-the-treatment-of-advanced-squamous-cell-lung-cancer-focus-on-afatinib
#17
REVIEW
Vera Hirsh
Until recently, few treatment options existed for the treatment of squamous cell carcinoma (SqCC) of the lung, especially in the second-line setting following platinum-based chemotherapy. Accordingly, outcomes in this subtype of non-small-cell lung cancer (NSCLC) were generally poor. In this context, the recent availability of the checkpoint inhibitors nivolumab and pembrolizumab, the anti-VEGFR2 antibody ramucirumab (combined with docetaxel), and the ErbB-family blocker afatinib for the treatment of relapsed/refractory SqCC of the lung represent major advances...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28536156/gefitinib-delays-nsclc-recurrence-after-surgery
#18
(no author information available yet)
For patients with non-small cell lung cancer and activating EGFR mutations who have had surgery, gefitinib appears to be more effective than chemotherapy in delaying disease recurrence. In a phase III trial, patients given the EGFR inhibitor were disease-free for 10 months longer than those who received chemotherapy.
May 23, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28493811/pooled-analysis-of-individual-patient-data-on-concurrent-chemoradiotherapy-for-stage-iii-non-small-cell-lung-cancer-in-elderly-patients-compared-with-younger-patients-who-participated-in-us-national-cancer-institute-cooperative-group-studies
#19
Thomas E Stinchcombe, Ying Zhang, Everett E Vokes, Joan H Schiller, Jeffrey D Bradley, Karen Kelly, Walter J Curran, Steven E Schild, Benjamin Movsas, Gerald Clamon, Ramaswamy Govindan, George R Blumenschein, Mark A Socinski, Neal E Ready, Wallace L Akerley, Harvey J Cohen, Herbert H Pang, Xiaofei Wang
Purpose Concurrent chemoradiotherapy is standard treatment for patients with stage III non-small-cell lung cancer. Elderly patients may experience increased rates of adverse events (AEs) or less benefit from concurrent chemoradiotherapy. Patients and Methods Individual patient data were collected from 16 phase II or III trials conducted by US National Cancer Institute-supported cooperative groups of concurrent chemoradiotherapy alone or with consolidation or induction chemotherapy for stage III non-small-cell lung cancer from 1990 to 2012...
May 11, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28492290/atezolizumab-a-novel-pd-l1-inhibitor-in-cancer-therapy-with-a-focus-in-bladder-and-non-small-cell-lung-cancers
#20
A Krishnamurthy, A Jimeno
In recent years, immunotherapy has come to the forefront as a major development in cancer treatment. Evasion of the immune system by tumor cells has been identified as one of the hallmarks of cancer and multiple therapies have been developed to counter this process. Programmed cell death 1 ligand 1 (PD-L1), a ligand to programmed cell death protein 1 (PD-1), is expressed by many cancer cells and the binding of PD-L1 to PD-1 results in the suppression of T-cell-mediated immune response against cancer cells. Atezolizumab is a monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1, thereby enhancing T-cell activity against tumor cells...
April 2017: Drugs of Today
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