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https://www.readbyqxmd.com/read/29777823/updated-efficacy-analysis-including-secondary-population-results-for-oak-a-randomized-phase-iii-study-of-atezolizumab-vs-docetaxel-in-patients-with-previously-treated-advanced-non-small-cell-lung-cancer
#1
L Fehrenbacher, J von Pawel, K Park, A Rittmeyer, D R Gandara, S Ponce Aix, J-Y Han, S M Gadgeel, T Hida, D L Cortinovis, M Cobo, D M Kowalski, F De Marinis, M Gandhi, B Danner, C Matheny, M Kowanetz, P He, F Felizzi, H Patel, A Sandler, M Ballinger, F Barlesi
INTRODUCTION: The efficacy and safety of atezolizumab vs docetaxel as second- or third-line treatment in patients with advanced non-small cell lung cancer in the primary (n=850; ITT850) and secondary (n=1225; ITT1225) efficacy populations of the randomized phase III OAK study at an updated data cutoff were assessed. METHODS: Patients received atezolizumab 1200mg or docetaxel 75mg/m2 intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively...
May 16, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29775807/fir-efficacy-safety-and-biomarker-analysis-of-a-phase-ii-open-label-study-of-atezolizumab-in-pd-l1-selected-patients-with-non-small-cell-lung-cancer
#2
David R Spigel, Jamie E Chaft, Scott Gettinger, Bo H Chao, Luc Dirix, Peter Schmid, Laura Q M Chow, Rodney J Hicks, Larry Leon, Jill Fredrickson, Marcin Kowanetz, Alan Sandler, Roel Funke, Naiyer A Rizvi
INTRODUCTION: The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced non-small-cell lung cancer (NSCLC) selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. METHODS: Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into Cohort 1 (chemotherapy-naïve/>6 months between adjuvant chemotherapy and recurrence), Cohort 2 (≥ second-line without brain metastases), or Cohort 3 (≥ second-line with treated brain metastases)...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29774061/immunotherapy-in-non-metastatic-non-small-cell-lung-cancer-can-the-benefits-of-stage-iv-therapy-be-translated-into-earlier-stages
#3
REVIEW
Griet Deslypere, Dorothée Gullentops, Els Wauters, Johan Vansteenkiste
Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor ( EGFR ) activating mutations or anaplastic lymphoma kinase ( ALK ) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29768118/final-overall-survival-analysis-from-a-study-comparing-first-line-crizotinib-with-chemotherapy-results-from-profile-1014
#4
Benjamin J Solomon, Dong-Wan Kim, Yi-Long Wu, Kazuhiko Nakagawa, Tarek Mekhail, Enriqueta Felip, Federico Cappuzzo, Jolanda Paolini, Tiziana Usari, Yiyun Tang, Keith D Wilner, Fiona Blackhall, Tony S Mok
Purpose The phase III PROFILE 1014 trial compared crizotinib with chemotherapy as first-line treatment in patients with anaplastic lymphoma kinase (ALK) -positive advanced nonsquamous non-small-cell lung cancer. Here, we report the final overall survival (OS) results. Patients and Methods Patients were randomly assigned to receive oral crizotinib 250 mg twice daily (n = 172) or intravenous pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin (area under the concentration-time curve of 5 to 6 mg·mL/min) every 3 weeks for a maximum of six cycles (n = 171)...
May 16, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29764596/-a-case-report-of-advanced-lung-adenocarcinoma-harboring-kras-mutation-treated-with-anlotinib
#5
Yudong Su, Zhaoting Meng, Xiaoyan Xu, XinYue Wang, Ran Zuo, Yunxia Hou, Kai Li, Peng Chen
In recent years, the number of advanced non-small cell lung cancer (NSCLC) patients has gradually increased, and the treatment methods have also been significantly increased. However, there are no standard treatment plans at home and abroad for third-line and above patients who are refractory to targeted therapy epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) or chemotherapy. The clinical treatment effect is also not satisfactory. Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit...
May 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29755953/first-line-treatment-in-egfr-mutant-non-small-cell-lung-cancer-is-there-a-best-option
#6
REVIEW
Ajaz Bulbul, Hatim Husain
First generation or second generation EGFR tyrosine kinase inhibitors are currently the standard of care for the first-line management of non-small cell lung cancer (NSCLC) patients with activating mutations within the kinase domain of the epidermal growth factor receptor gene (1, 2). Resistance to targeted therapy can develop after 9-11 months (3-8). Third generation inhibitors were developed to target the EGFR T790M clone, which is the most common dominant second site resistance mutation after first or second generation inhibitors...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29751136/anti-epidermal-growth-factor-vaccine-antibodies-enhance-the-efficacy-of-tyrosine-kinase-inhibitors-and-delay-the-emergence-of-resistance-in-egfr-mutant-lung-cancer-cells
#7
Jordi Codony-Servat, Silvia García-Roman, Miguel Ángel Molina-Vila, Jordi Bertran-Alamillo, Ana Giménez-Capitán, Santiago Viteri, Andrés F Cardona, Erik d'Hondt, Niki Karachaliou, Rafael Rosell
INTRODUCTION: Mutations in EGFR correlate with impaired response to immune checkpoint inhibitors and the development of novel immunotherapeutic approaches for EGFR mutant non-small cell lung cancer (NSCLC) is of particular interest. Immunization against EGF has demonstrated efficacy in a phase III trial including unselected NSCLC patients, but little was known about the mechanisms involved in the effects of the anti-EGF antibodies generated by vaccination (anti-EGF VacAbs) or their activity in tumor cells with EGFR mutations...
May 8, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29744867/p-glycoprotein-mdr1-abcb1-restricts-brain-accumulation-and-cytochrome-p450-3a-cyp3a-limits-oral-availability-of-the-novel-alk-ros1-inhibitor-lorlatinib
#8
Wenlong Li, Rolf W Sparidans, Yaogeng Wang, Maria C Lebre, Els Wagenaar, Jos H Beijnen, Alfred H Schinkel
Lorlatinib (PF-06463922) is a promising oral anaplastic lymphoma kinase (ALK) and ROS1 inhibitor currently in Phase III clinical trials for treatment of non-small cell lung cancer (NSCLC) containing an ALK rearrangement. With therapy-resistant brain metastases a major concern in NSCLC, lorlatinib was designed to have high membrane and blood-brain barrier permeability. We investigated the roles of the multidrug efflux transporters ABCB1 and ABCG2, and the multispecific drug-metabolizing enzyme CYP3A in plasma pharmacokinetics and tissue distribution of lorlatinib using genetically modified mouse strains...
May 9, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29733770/patient-reported-symptoms-and-impact-of-treatment-with-osimertinib-versus-chemotherapy-in-advanced-non-small-cell-lung-cancer-the-aura3-trial
#9
Chee Khoon Lee, Silvia Novello, Anna Rydén, Helen Mann, Tony Mok
Purpose Capturing patient-reported outcome data is important for evaluating the overall clinical benefits of new cancer therapeutics. We assessed self-reported symptoms of advanced non-small-cell lung cancer in patients treated with osimertinib or chemotherapy in the AURA3 phase III trial. Patients and Methods Patients completed the European Organisation for Research and Treatment of Cancer 13-item Quality of Life Questionnaire-Lung Cancer Module (EORTC QLQ-LC13) questionnaire on disease-specific symptoms and the EORTC 30-item Core Quality of Life Questionnaire (EORTC QLC-C30) on general cancer symptoms, functioning, global health status, and quality of life...
May 7, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29731344/prognostic-value-%C3%A2-of-lung-cancer-subscale-in-older-patients-with-advanced-non-small-cell-lung-cancer-an-integrated-analysis-of-jcog0207-and-jcog0803-wjog4307l-jcog1414a
#10
Tomonori Mizutani, Masahiko Ando, Junki Mizusawa, Kenichi Nakamura, Haruhiko Fukuda, Hiroko Tsukada, Tetsuya Abe, Koji Takeda, Akira Yokoyama, Shinichiro Nakamura, Kazuhiko Nakagawa, Noboru Yamamoto, Yuichiro Ohe
OBJECTIVE: The Lung Cancer Subscale (LCS) of the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire is commonly used for evaluating lung cancer-specific symptoms. The objective of this study was to elucidate the prognostic value of the LCS in older patients with advanced non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: We conducted an integrated analysis of data from two randomized phase III trials (JCOG0207, JCOG0803/WJOG4307L) including patients aged 70 years or older with advanced NSCLC to evaluate the prognostic value of LCS scores at baseline (Aim 1) and for symptom improvement (an increase in LCS of two points or more during treatment) (Aim 2)...
May 3, 2018: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/29728800/phase-ii-trial-of-induction-chemotherapy-of-pemetrexed-plus-split-dose-cisplatin-followed-by-pemetrexed-maintenance-for-untreated-non-squamous-non-small-cell-lung-cancer
#11
Taro Koba, Seigo Minami, Yu Nishijima-Futami, Kentaro Masuhiro, Hiromi Kimura, Shinji Futami, Moto Yaga, Masahide Mori, Hiroyuki Kagawa, Takeshi Uenami, Satoshi Kohmo, Tomoyuki Otsuka, Suguru Yamamoto, Kiyoshi Komuta, Takashi Kijima
PURPOSE: We conducted a phase II trial to evaluate the efficacy and safety of induction chemotherapy of pemetrexed plus split-dose cisplatin followed by pemetrexed maintenance for advanced non-squamous non-small-cell lung cancer (NSCLC). METHODS: Patients with advanced or recurrent untreated non-squamous NSCLC received split-dose cisplatin (40 mg/m2 , days 1 and 8) plus pemetrexed (500 mg/m2 , day 1) tri-weekly. After four cycles of induction, patients without disease progression received pemetrexed maintenance until disease progression or unacceptable toxicity...
May 4, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29696478/concurrent-chemoradiation-for-locally-advanced-stage-iii-non-small-cell-lung-cancer-with-cisplatin-vinorelbine-and-thoracic-radiotherapy-a-phase-ii-study-from-the-galician-lung-cancer-group
#12
M Costa Rivas, G Huidobro Vence, J L Fírvida Pérez, B Campos Balea, J García Gonzalez, M Lázaro Quintela, M Caeiro Muñoz, B Taboada Valladares, J E Castro Gómez, S Vázquez Estevez, F J Afonso Afonso, C Azpitarte Raposeiras, M Amenedo Gancedo, J Casal Rubio
PURPOSE: The aim of this phase II study was to evaluate the activity and safety of the combination of cisplatin and vinorelbine with thoracic radiotherapy in unresectable locally advanced stage III non-small cell lung cancer (NSCLC). The primary endpoint was the objective response rate (ORR). Secondary objectives included toxicity profile, progression-free survival (PFS), and overall survival (OS). MATERIALS AND METHODS: A total of 48 NSCLC patients were enrolled (median age 60 years, 52% stage IIIA and 48% stage IIIB, 52% adenocarcinoma)...
April 25, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29687154/erlotinib-in-routine-clinical-practice-for-first-line-maintenance-therapy-in-patients-with-advanced-non-small-cell-lung-cancer-nsclc
#13
M Faehling, J Achenbach, P Staib, U Steffen, H W Tessen, V E Gaillard, W Brugger
PURPOSE: The controlled phase III trial SATURN demonstrated that maintenance therapy with erlotinib after the first-line platinum-based chemotherapy prolonged progression-free survival (PFS) and overall survival (OS) of non-small cell lung cancer (NSCLC) patients with advanced, non-progressive disease. We conducted the non-interventional study SATURN NIS to investigate the effectiveness and tolerability of erlotinib maintenance in daily clinical practice. METHODS: This single-arm NIS screened 290 patients with locally advanced or metastatic NSCLC (stage IIIB or IV) and stable disease after standard platinum-based first-line chemotherapy in 95 institutions across Germany...
April 23, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29685883/a-model-of-overall-survival-predicts-treatment-outcomes-with-atezolizumab-vs-chemotherapy-in-non-small-cell-lung-cancer-based-on-early-tumor-kinetics
#14
Laurent Claret, Jin Y Jin, Charles Ferté, Helen Winter, Sandhya Girish, Mark Stroh, Pei He, Marcus Ballinger, Alan Sandler, Amita Joshi, Achim Rittmeyer, David R Gandara, Jean-Charles Soria, René Bruno
PURPOSE: Standard endpoints often poorly predict overall survival (OS) with immunotherapies. We investigated the predictive performance of model-based tumor growth inhibition (TGI) metrics using data from atezolizumab clinical trials in patients with non-small cell lung cancer. METHODS: OS benefit with atezolizumab vs docetaxel was observed in both POPLAR (phase II) and OAK (phase III) although progression-free survival was similar between arms. A multivariate model linking baseline patient characteristics and on-treatment tumor growth rate constant (KG), estimated using time profiles of sum of longest diameters (RECIST 1...
April 23, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29684049/clinical-factors-associated-with-early-progression-and-grade-3-4-toxicity-in-patients-with-advanced-non-small-cell-lung-cancers-treated-with-nivolumab
#15
Coraline Dumenil, Marie-Ange Massiani, Jennifer Dumoulin, Violaine Giraud, Sylvie Labrune, Thierry Chinet, Etienne Giroux Leprieur
INTRODUCTION: The prognosis of advanced non-small-cell lung cancer (NSCLC) has been improved by development of immune checkpoint inhibitors (ICIs) such as nivolumab for second-line treatment. As phase III trials include only selected patients, we here investigated the clinical factors associated with efficacy and safety of nivolumab in 'real life' patients with advanced NSCLC. METHODS: Clinical and histological characteristics, therapies and survival data of all consecutive patients with advanced NSCLC included prospectively and treated by nivolumab in two French academic hospitals between February 2015 and December 2016 were examined...
2018: PloS One
https://www.readbyqxmd.com/read/29682899/generalization-and-representativeness-of-phase-iii-immune-checkpoint-blockade-trials-in-non-small-cell-lung-cancer
#16
Shin Hye Yoo, Bhumsuk Keam, Miso Kim, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo
BACKGROUND: Strict eligibility criteria for patient enrollment in phase III trials raise questions regarding generalization to ineligible patients. We evaluated whether pivotal phase III trials of immune checkpoint blockades (ICBs) represent the overall population of non-small cell lung cancer (NSCLC) patients. METHODS: We reviewed the inclusion and exclusion criteria of three phase III trials (CheckMate057, CheckMate017, and KEYNOTE-010). Stage IIIB or IV NSCLC patients diagnosed from 2011 to 2013 at Seoul National University Hospital (cohort 1) were reviewed...
April 22, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29682332/gender-and-outcomes-in-non-small-cell-lung-cancer-an-old-prognostic-variable-comes-back-for-targeted-therapy-and-immunotherapy
#17
Joseph A Pinto, Carlos S Vallejos, Luis E Raez, Luis A Mas, Rossana Ruiz, Junior S Torres-Roman, Zaida Morante, Jhajaira M Araujo, Henry L Gómez, Alfredo Aguilar, Denisse Bretel, Claudio J Flores, Christian Rolfo
Background: There are well-known differences in gender outcome in non-small cell lung cancer (NSCLC) and other cancers. In this work, we evaluated several randomised clinical trials to explore the gender influence in the outcome of patients with NSCLC treated with targeted therapy and immunotherapy. Methods: We performed a series of meta-analysis to compare the gender outcome in the routine setting for overall survival and progression-free survival (PFS) in phase III randomised clinical trials comparing EGFR inhibitors versus chemotherapy (OPTIMAL, LUX-lung 3, LUX-lung 6, EURTAC, ENSURE and WTJOG); ALK inhibitors versus chemotherapy (ASCEND 4, ASCEND 5, PROFILE 1014 and NCT009323893) and anti-PD1 checkpoint inhibitors versus chemotherapy (CheckMate 017, CheckMate 026, CheckMate 057, KEYNOTE 010 and KEYNOTE 024)...
2018: ESMO Open
https://www.readbyqxmd.com/read/29668860/alectinib-versus-chemotherapy-in-crizotinib-pretreated-anaplastic-lymphoma-kinase-alk-positive-non-small-cell-lung-cancer-results-from-the-phase-iii-alur-study
#18
S Novello, J Mazières, I-J Oh, J de Castro, M R Migliorino, Å Helland, R Dziadziuszko, F Griesinger, A Kotb, A Zeaiter, A Cardona, B Balas, H K Johannsdottir, A Das-Gupta, J Wolf
Background: This is the first trial to directly compare efficacy and safety of alectinib versus standard chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients who have progressed on, or were intolerant to, crizotinib. Patients and methods: ALUR (MO29750; NCT02604342) was a randomized, multicenter, open-label, phase III trial of alectinib versus chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive NSCLC patients previously treated with platinum-based doublet chemotherapy and crizotinib...
April 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29666135/study-protocol-for-the-saron-trial-a-multicentre-randomised-controlled-phase-iii-trial-comparing-the-addition-of-stereotactic-ablative-radiotherapy-and-radical-radiotherapy-with-standard-chemotherapy-alone-for-oligometastatic-non-small-cell-lung-cancer
#19
John Conibear, Brendan Chia, Yenting Ngai, Andrew Tom Bates, Nicholas Counsell, Rushil Patel, David Eaton, Corinne Faivre-Finn, John Fenwick, Martin Forster, Gerard G Hanna, Susan Harden, Philip Mayles, Syed Moinuddin, David Landau
INTRODUCTION: Following growing evidence to support the safety, local control (LC) and potential improvement in overall survival (OS) in patients with oligometastatic non-small cell lung cancer (NSCLC) that have been treated with local ablative therapy such as stereotactic ablative radiotherapy (SABR) and stereotactic radiosurgery (SRS), we initiate the SARON trial to investigate the impact and feasibility of adding SABR/SRS and radical radiotherapy (RRT) following standard chemotherapy on OS...
April 17, 2018: BMJ Open
https://www.readbyqxmd.com/read/29661758/high-tmb-predicts-immunotherapy-benefit-in-nsclc
#20
(no author information available yet)
The first data from the phase III CheckMate-227 trial of ipilimumab plus nivolumab for the treatment of non-small cell lung cancer suggests that the two drugs boost progression-free survival in patients with a high tumor mutation burden. After 1 year, progression-free survival was 43% for patients treated with the checkpoint inhibitor combination, compared with 13% for patients treated with chemotherapy.
April 16, 2018: Cancer Discovery
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