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Lung cancer third line therapy

Manami Sazuka, Yoko Murano, Kazufumi Takada, Keisuke Nonaka, Hirokazu Yamada, Hiroshi Yamamoto
BACKGROUND: Whether or not immune checkpoint inhibitors are safe and effective for the elderly remains unclear, even though these drugs were approved two years ago for the treatment of advanced non-small cell lung cancer in Japan. Older cancer patients are vulnerable to chemotherapy, so their life function should be closely monitored before starting, continuing, or discontinuing cancer treatment. CASE: An 85-year-old man showed a wedge-shaped shadow in the apical portion of the left lung on chest computed tomography...
2018: Nihon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics
Maximilian J Hochmair, Anna Buder, Sophia Schwab, Otto C Burghuber, Helmut Prosch, Wolfgang Hilbe, Agnieszka Cseh, Richard Fritz, Martin Filipits
BACKGROUND: Acquired epidermal growth factor receptor (EGFR) T790M mutation is the primary resistance mechanism to first-generation EGFR tyrosine kinase inhibitors (TKIs) used in advanced, EGFR mutation-positive non-small-cell lung cancer (NSCLC). Available data, predominantly in Asian patients, suggest that this mutation is also the major cause of resistance to the irreversible ErbB family blocker, afatinib. For EGFR T790M-positive patients who progress on EGFR TKI therapy, osimertinib is an effective treatment option...
December 12, 2018: Targeted Oncology
Mika Saigusa, Kazuhiro Asada, Taisuke Akamatsu, Yuko Tanaka, Yoshinari Endo, Akito Yamamoto, Satoru Morita, Toshihiro Shirai
BACKGROUND: There are no standard cytotoxic treatments for non-small-cell lung cancer (NSCLC) patients beyond third-line therapy. The purpose of this study was to evaluate the efficacy and safety of amrubicin in pretreated NSCLC patients. METHODS: The records of NSCLC patients who received amrubicin monotherapy as a third or later line of chemotherapy at Shizuoka General Hospital between April 2007 and March 2015 were retrospectively reviewed. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1...
December 12, 2018: Oncology Research and Treatment
David Campbell, Ken O'Day, Nadine Hertel, John R Penrod, Melinda Manley Daumont, Michael Lees
BACKGROUND: The burden of advanced non-small cell lung cancer (NSCLC) is not well understood, and the number of patients likely to receive treatment in Europe has not been quantified. The aim of this study was to forecast the annual number of patients with squamous and non-squamous advanced NSCLC likely to receive second and third lines of therapy (LOT) from 2016 to 2020 in France, Germany, Italy, and Spain. METHODS: A patient count model (PCM) was developed in Microsoft Excel to estimate the number of patients with refractory advanced NSCLC eligible to receive systemic treatment...
November 26, 2018: Population Health Metrics
B Melosky, P Cheema, J Agulnik, R Albadine, D G Bebb, N Blais, R Burkes, C Butts, P B Card, A M Y Chan, V Hirsh, D N Ionescu, R Juergens, W Morzycki, Z Poonja, R Sangha, M Tehfe, M S Tsao, M Vincent, Z Xu, G Liu
Background: Inhibition of the anaplastic lymphoma kinase (alk) oncogenic driver in advanced non-small-cell lung carcinoma (nsclc) improves survival. In 2015, Canadian thoracic oncology specialists published a consensus guideline about the identification and treatment of ALK- positive patients, recommending use of the alk inhibitor crizotinib in the first line. New scientific literature warrants a consensus update. Methods: Clinical trials of alk inhibitor were reviewed to assess benefits, risks, and implications relative to current Canadian guidance in patients with ALK- positive nsclc...
October 2018: Current Oncology
Takayuki Jodai, Chieko Yoshida, Ryo Sato, Yosuke Kakiuchi, Nahoko Sato, Shinji Iyama, Tomoko Kimura, Koichi Saruwatari, Sho Saeki, Hidenori Ichiyasu, Kazuhiko Fujii, Yusuke Tomita
INTRODUCTION: The impact of immune checkpoint blockade on immunity in cancer patients is not completely elucidated due to the complexity of the immune network. Recent studies have revealed a significant role of programed cell death-ligand 2 (PD-L2) in negatively controlling the production of CD4+ T helper type 2 (Th2) cytokines and airway hypersensitiveness, suggesting hypo-responsive Th2 cells via the PD-1/PD-L2 inhibitory pathway in lung could be reawaken by PD-1 blockade therapy. METHODS: We describe the first report of acute eosinophilic pneumonia (AEP), which is known as Th2-associated pulmonary disease, triggered by nivolumab, an anti-PD-1 antibody, in an advanced non-small cell lung cancer patient...
November 21, 2018: Immunity, Inflammation and Disease
Nan Zhang, Nan Guo, Liang Tian, Zhigang Miao
Purpose: We performed a systematic review and meta-analysis to investigate the efficacy of third-line treatment for advanced non-small-cell lung cancer (NSCLC). Materials and Methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials (RCTs) assessing third-line therapy in advanced NSCLC patients were included. Outcomes of interest included overall survival (OS) and progression-free survival (PFS)...
October 23, 2018: Oncotarget
Jimmy Van den Eynden, Ganesh Umapathy, Arghavan Ashouri, Diana Cervantes-Madrid, Joanna Szydzik, Kristina Ruuth, Jan Koster, Erik Larsson, Jikui Guan, Ruth H Palmer, Bengt Hallberg
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that is a clinical target of major interest in cancer. Mutations and rearrangements in ALK trigger the activation of the encoded receptor and its downstream signaling pathways. ALK mutations have been identified in both familial and sporadic neuroblastoma cases as well as in 30 to 40% of relapses, which makes ALK a bona fide target in neuroblastoma therapy. Tyrosine kinase inhibitors (TKIs) that target ALK are currently in clinical use for the treatment of patients with ALK-positive non-small cell lung cancer...
November 20, 2018: Science Signaling
Laura Mezquita, Andreea Varga, David Planchard
Osimertinib is a third-generation EGFR-TKI, specifically designed to inhibit EGFR sensitizing and T790M acquired mutations, minimizing exposure in EGFR-wildtype tissues. Areas covered: Osimertinib use in EGFR-mutated NSCLC patients is described, focusing on safety and tolerability from studies supporting its approval. Expert opinion: Osimertinib demonstrated greater efficacy, including CNS activity, compared to chemotherapy, with a manageable safety profile in pretreated T790M+ EGFR-mutated patients, leading to FDA approval in 2015 within record time in the oncology field...
November 20, 2018: Expert Opinion on Drug Safety
Julia Roeper, Frank Griesinger
PURPOSE OF REVIEW: Epidermal growth factor receptor (EGFR) mt+ nonsmall cell lung cancer (NSCLC) were the first molecularly described NSCLC with an established 'targeted' therapy inhibiting mutated EGFR [EGFR tyrosine kinase inhibitor (TKI)]. EGFR TKI of first and second generation have led to an unprecedented improvement in objective response rate, progression-free survival (PFS) and overall survival (OS) compared with chemotherapy with a significantly reduced toxicity and improved quality of life...
January 2019: Current Opinion in Oncology
Hiroshige Yoshioka, Yoshihito Kogure, Masahiko Ando, Chiyoe Kitagawa, Masahiro Iwasaku, Takashi Niwa, Hideo Saka
BACKGROUND: Amrubicin hydrochloride is administered as second- or third-line therapy for small cell lung cancer, and is known to cause severe myelotoxicity. This study evaluated the efficacy and safety of weekly amrubicin for refractory/relapsed small cell lung cancer. PATIENTS AND METHODS: A single-arm, open-label, multicenter, phase II study of weekly amrubicin was performed in 21 patients at seven centers in Japan from 2012 through 2015. RESULTS: A partial response (PR) was noted in one out of the first 18 patients...
November 2018: In Vivo
Kathleen M Aguilar, Katherine B Winfree, Catherine E Muehlenbein, Yajun Emily Zhu, Thomas Wilson, Stewart Wetmore, Eric S Nadler
INTRODUCTION: Targeted therapies, including tyrosine kinase inhibitors (TKIs) that target the sensitizing epidermal growth factor receptor (EGFR) gene are recommended for patients with non-small cell lung cancer (NSCLC). Most patients with NSCLC who test positive for the EGFR mutation and receive TKIs develop resistance to these drugs. Questions remain regarding which treatment sequence is optimal for patients with EGFR-mutant NSCLC, and few studies have evaluated patterns of TKI treatment use in NSCLC, irrespective of EGFR mutation status, in a real-world setting...
October 19, 2018: Advances in Therapy
Sara Redaelli, Monica Ceccon, Marina Zappa, Geeta G Sharma, Cristina Mastini, Mario Mauri, Marion Nigoghossian, Luca Massimino, Nicoletta Cordani, Francesca Farina, Rocco Piazza, Carlo Gambacorti-Passerini, Luca Mologni
Targeted therapy changed the standard of care in ALK-dependent tumors. However, resistance remains a major challenge. Lorlatinib is a third generation ALK inhibitor that inhibits most ALK mutants resistant to current ALK inhibitors. In this study, we utilize lorlatinib-resistant anaplastic large cell lymphoma (ALCL), non-small cell lung cancer (NSCLC), and neuroblastoma cell lines in vitro and in vivo to investigate the acquisition of resistance and its underlying mechanisms. ALCL cells acquired compound ALK mutations G1202R/G1269A and C1156F/L1198F in vitro at high drug concentrations...
October 15, 2018: Cancer Research
Zhiwei Sun, Shixia Zhou, Junling Tang, Ting Ye, Jingyuan Li, Doudou Liu, Jian Zhou, Jianyu Wang, H Rosie Xing
BACKGROUND: Cancer treatment is based on tumor staging. Curative intent is only applied to localized tumors. Recent studies show that oligometastatic patients who have limited number of metastases may benefit from metastasis-directed local treatments to achieve long-term survival. However, mechanisms underlying oligometastatic to polymetastatic progression remains elusive. METHODS: The effects of miR-200c and Sec23a on tumor metastasis were verified both in vitro and in vivo...
October 6, 2018: EBioMedicine
Jessica Davies, Michael Martinec, Mathieu Coudert, Paul Delmar, Gracy Crane
BACKGROUND: The anaplastic lymphoma kinase (ALK) treatment landscape is crowded following recent ALK inhibitor approvals, and updated information on real-world treatment patterns in advanced non-small-cell lung cancer (aNSCLC) with ALK rearrangement (ALK+) is needed. METHODS: This retrospective US cohort study used Flatiron Health's longitudinal electronic health record (EHR)-derived database. Patients (≥18 years old) diagnosed with stage IIIB/IV aNSCLC, with documented ALK rearrangement and ≥2 visits after January 1, 2011 were followed until February 28, 2016...
October 8, 2018: Current Medical Research and Opinion
Akiko Takahashi, Masahiro Seike, Mika Chiba, Satoshi Takahashi, Shinji Nakamichi, Masaru Matsumoto, Susumu Takeuchi, Yuji Minegishi, Rintaro Noro, Shinobu Kunugi, Kaoru Kubota, Akihiko Gemma
Overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is critical in combating EGFR-mutant non-small cell lung cancer (NSCLC). We tried to construct a novel therapeutic strategy to conquer the resistance to second-and third-generation EGFR-TKIs in EGFR-positive NSCLC patients. We established afatinib- and osimertinib-resistant lung adenocarcinoma cell lines. Exome sequencing, cDNA array and miRNA microarray were performed using the established cell lines to discover novel therapeutic targets associated with the resistance to second-and third-generation EGFR-TKIs...
October 5, 2018: Scientific Reports
Jin-Min Xue, Manirakiza Astère, Mao-Xi Zhong, Han Lin, Jin Shen, Yu-Xi Zhu
Apatinib (Aitan® , brand name in China) is a new anti-antiangiogenic agent that has recently been approved for the treatment of advanced gastric cancer (GC) in China. Nevertheless, its therapeutic efficacy against other types of advanced solid tumors remains unclear. This meta-analysis examines the short-term efficacy and safety of apatinib or combination therapy for GC, hepatocellular carcinoma (HCC) and non-small-cell lung cancer (NSCLC); and provides a discussion of its anti-angiogenesis therapy applications...
2018: OncoTargets and Therapy
Jan A Stratmann, Sebastian Michels, Sofia Hornetz, Daniel C Christoph, Sandra Sackmann, Werner Spengler, Helge Bischoff, Monica Schäfer, Jürgen Alt, Annette Müller, Eckart Laack, Martin Kimmich, Frank Griesinger, Martin Sebastian
PURPOSE: Osimertinib, a third-generation irreversible mutant-selective inhibitor of EGFR kinase activity was clinically evaluated in the AURA trials, where it showed high clinical efficacy and a favorable toxicity profile in patients with acquired exon 20-EGFR pT790M mutation. We provide the clinical data of the German expanded access program that further characterizes the efficacy and safety of osimertinib in a heterogeneous patient population outside clinical trials. METHODS: We performed a retrospective data analysis on patients who were included into the German osimertinib EAP...
December 2018: Journal of Cancer Research and Clinical Oncology
Cesare Gridelli, Javier de Castro Carpeno, Anne-Marie C Dingemans, Frank Griesinger, Francesco Grossi, Corey Langer, Yuichiro Ohe, Konstantinos Syrigos, Nick Thatcher, Ashis Das-Gupta, Matt Truman, Margarita Donica, Vlatka Smoljanovic, Jaafar Bennouna
Importance: Bevacizumab treatment beyond progression has been investigated in breast and metastatic colorectal cancers. Avastin in All Lines Lung (AvaALL) is the first randomized phase 3 study of bevacizumab across multiple lines of treatment beyond progression in non-small cell lung cancer (NSCLC). Objective: To assess the efficacy and safety of continuous bevacizumab treatment beyond first progression in NSCLC. Design, Setting, and Participants: AvaALL was a randomized, open-label, phase 3b trial, conducted from 2011 to 2015 in 123 centers worldwide...
August 30, 2018: JAMA Oncology
Tao Jiang, Chunxia Su, Shengxiang Ren, Federico Cappuzzo, Gaetano Rocco, Joshua D Palmer, Nico van Zandwijk, Fiona Blackhall, Xiuning Le, Nathan A Pennell, Caicun Zhou
The first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have brought substantial clinical benefit to patients with advanced non-small cell lung cancer (NSCLC) and sensitizing EGFR mutation. However, acquired resistance is inevitable since the vast majority of patients experience disease relapse within ~1-2 years. Osimertinib is a novel irreversible, covalent third-generation EGFR-TKI and potent inhibitor of EGFR T790M mutation, the most common mechanism of acquired resistance to first-generation EGFR-TKIs...
July 2018: Journal of Thoracic Disease
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