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Lung cancer third line therapy

Jason C Hsu, Chen-Fang Wei, Szu-Chun Yang
INTERVENTIONS: Targeted therapies have been proven to provide clinical benefits to patients with metastatic non-small cell lung cancer (NSCLC). Gefitinib was initially approved and reimbursed as a third-line therapy for patients with advanced NSCLC by the Taiwan National Health Insurance (NHI) in 2004; subsequently it became a second-line therapy (in 2007) and further a first-line therapy (in 2011) for patients with epidermal growth factor receptor mutation-positive advanced NSCLC. Another targeted therapy, erlotinib, was initially approved as a third-line therapy in 2007, and it became a second-line therapy in 2008...
March 15, 2019: BMJ Open
Tri Le, David E Gerber
The FLAURA trial established osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), as a viable first-line therapy in non-small cell lung cancer (NSCLC) with sensitizing EGFR mutations, namely exon 19 deletion and L858R. In this phase 3 randomized, controlled, double-blind trial of treatment-naïve patients with EGFR mutant NSCLC, osimertinib was compared to standard-of-care EGFR TKIs (i.e., erlotinib or gefinitib) in the first-line setting. Osimertinib demonstrated improvement in median progression-free survival (18...
March 15, 2019: Cancers
Emiliano Calvo, Jong-Seok Lee, Sang-We Kim, Victor Moreno, Javier deCastro Carpeno, Doris Weilert, Gianluca Laus, Helen Mann, Karthick Vishwanathan
Osimertinib is a potent, third-generation, irreversible, central nervous system active epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that selectively inhibits EGFR-TKI sensitizing and EGFR T790M resistance mutations. It is approved for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, and for patients with T790M-positive advanced NSCLC whose disease has progressed on or after EGFR-TKI therapy...
March 15, 2019: Journal of Clinical Pharmacology
Shun Lu
Lung cancer is the leading cause of cancer death in China, and approximately one third of these cancers are squamous cell carcinoma (SqCC) of the lung. Ethnic diversity and country-specific environmental factors can account for interindividual variations in response to and tolerability of anticancer therapies. Although several targeted therapies have recently been approved for patients with relapsed/refractory SqCC of the lung, only afatinib, an irreversible ErbB family blocker, has data of Chinese patients...
2019: OncoTargets and Therapy
Hong-Joon Shin, Bo Gun Kho, Min-Seok Kim, Ha Young Park, Tae-Ok Kim, Yu-Il Kim, Sung-Chul Lim, Cheol-Kyu Park, Young-Chul Kim, Yoo-Duk Choi, In-Jae Oh
RATIONALE: Current guidelines for advanced non-small cell lung cancer (NSCLC) recommend the use of targeted agents for specific driver genes after confirming genetic alterations. Although epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement are usually mutually exclusive, EGFR and ALK co-alterations have been reported increasingly in cases of NSCLC. However, the optimal treatment for these cases has not been established. PATIENT CONCERNS: This case series describes three patients diagnosed with advanced non-squamous NSCLC who harbored EGFR and ALK co-alterations...
March 2019: Medicine (Baltimore)
Benjamin P Brown, Yun-Kai Zhang, David Westover, Yingjun Yan, Huan Qiao, Vincent Huang, Zhenfang Du, Jarrod A Smith, Jeffrey S Ross, Vincent A Miller, Siraj M Ali, Lyudmila Bazhenova, Alexa B Schrock, Jens Meiler, Christine M Lovly
PURPOSE: The third-generation EGFR inhibitor, osimertinib, is the first mutant selective inhibitor that has received regulatory approval for the treatment of patients with EGFR -mutant lung cancer. Despite the development of highly selective third-generation inhibitors, acquired resistance remains a significant clinical challenge. Recently, we and others have identified a novel osimertinib resistance mutation, G724S, which was not predicted in in vitro screens. Here, we investigate how G724S confers resistance to osimertinib...
February 22, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Véronique Hofman, Paul Hofman
Patients with advanced or metastatic forms of lung cancer with an activating mutation in epidermal growth factor receptor ( EGFR ) are given tyrosine kinase inhibitors (TKIs) targeted therapies that are more efficient than chemotherapy. These patients are excluded from first-line immunotherapy. After a phase of regression these tumors develop systematically resistance requiring a rapid change in therapy. At present two strategies are being discussed. The first strategy, so called "historical' sequential treatment strategy, is based on the administration of first- or second-generation TKIs until the emergence of therapeutic resistance and, in the case of a EGFR T790M mutation, on the administration of third-generation TKIs...
January 2019: Journal of Thoracic Disease
Ayesha Murtuza, Ajaz Bulbul, John Paul Shen, Parissa Keshavarzian, Brian D Woodward, Fernando J Lopez-Diaz, Scott M Lippman, Hatim Husain
EGFR-activating mutations are observed in approximately 15% to 20% of patients with non-small cell lung cancer. Tyrosine kinase inhibitors have provided an illustrative example of the successes in targeting oncogene addiction in cancer and the role of tumor-specific adaptations conferring therapeutic resistance. The compound osimertinib is a third-generation tyrosine kinase inhibitor, which was granted full FDA approval in March 2017 based on targeting EGFR T790M resistance. The compound has received additional FDA approval as first-line therapy with improvement in progression-free survival by suppressing the activating mutation and preventing the rise of the dominant resistance clone...
February 15, 2019: Cancer Research
Koichi Saruwatari, Ryo Sato, Shunya Nakane, Shinya Sakata, Koutaro Takamatsu, Takayuki Jodai, Remi Mito, Yuko Horio, Sho Saeki, Yusuke Tomita, Takuro Sakagami
BACKGROUND: Anti-programmed cell death 1 (PD-1) monoclonal antibodies (Abs) unleash an immune response to cancer. However, a disruption of the immune checkpoint function by blocking PD-1/PD-ligand 1(PD-L1) signaling may trigger myasthenia gravis (MG) as a life-threatening immune-related adverse event. MG is a neuromuscular disease and is closely associated with being positive for anti-acetylcholine receptor (anti-AChR) Abs, which are high specific and diagnostic Abs for MG. METHODS: A 72-year-old man was diagnosed with chemotherapy-refractory lung squamous cell carcinoma and nivolumab was selected as the third-line regimen...
January 24, 2019: Cancers
Anna D Coutinho, Manan Shah, Orsolya E Lunacsek, Michael Eaddy, Joanne P Willey
OBJECTIVES: To evaluate treatment patterns, physician-assessed overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) among third-line (3L)-plus small cell lung cancer (SCLC) patients. MATERIALS AND METHODS: Retrospective analysis of a United States (US)-based community oncology electronic medical record (EMR) database was conducted. Target sample included SCLC patients ≥18 years of age whose disease progressed after at least 2 prior treatments...
January 2019: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Johan Pluvy, Solenn Brosseau, Sandrine Stelianides, Claire Danel, Marina Nguenang, Antoine Khalil, Bruno Crestani, Gérard Zalcman, Valérie Gounant
BACKGROUND: Sporadic lymphangioleiomyomatosis (LAM) is a rare form of diffuse parenchymal lung disease. PD-1 blocking antibodies constitute an essential treatment option for advanced non-small-cell lung cancer (NSCLC). The effect of immune checkpoint inhibitors in lymphangioleiomyomatosis patients with non-small cell lung cancer is unknown: concomitant symptomatic interstitial lung disease or the use of immunosuppressors was a key exclusion criterion in the original studies of immune checkpoint inhibitors, especially regarding the risk of interstitial lung disease exacerbation...
January 11, 2019: BMC Pulmonary Medicine
Jun Lu, Hua Zhong, Tianqing Chu, Xueyan Zhang, Rong Li, Jiayuan Sun, Runbo Zhong, Yuqin Yang, Mohammad Shah Alam, Yuqing Lou, Jianlin Xu, Yanwei Zhang, Jun Wu, Xiaowei Li, Xiaodong Zhao, Kai Li, Liming Lu, Baohui Han
BACKGROUND: Anlotinib has been demonstrated in clinical trials to be effective in prolonging the progression-free survival (PFS) and overall survival (OS) of refractory advanced non-small cell lung cancer (NSCLC) patients. However, the underlying molecular mechanisms and predictive biomarkers of anlotinib are still unclear. METHODS: A retrospective analysis of anlotinib administered to 294 NSCLC patients was performed to screen for underlying biomarkers of anlotinib-responsive patients...
December 21, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
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
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