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Lung cancer third line therapy

Baohui Han, Kai Li, Qiming Wang, Li Zhang, Jianhua Shi, Zhehai Wang, Ying Cheng, Jianxing He, Yuankai Shi, Yizhuo Zhao, Hao Yu, Yang Zhao, Weiqiang Chen, Yi Luo, Lin Wu, Xiuwen Wang, Robert Pirker, Kejun Nan, Faguang Jin, Jian Dong, Baolan Li, Yan Sun
Importance: Anlotinib is a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling. A phase 2 trial showed anlotinib to improve progression-free survival with a potential benefit of overall survival, leading to the phase 3 trial to confirm the drug's efficacy in advanced non-small cell lung cancer (NSCLC). Objective: To investigate the efficacy of anlotinib on overall survival of patients with advanced NSCLC progressing after second-line or further treatment...
August 9, 2018: JAMA Oncology
Rachel Ryu, Kristina E Ward
Purpose: Atezolizumab is a programmed death ligand 1 (PDL-1) blocking antibody that was approved for metastatic non-small cell lung cancer (NSCLC) in patients with disease progression. Various studies have been initiated to explore the effectiveness of atezolizumab among different patient cohorts and disease statuses, including as first-line therapy. The purpose of this paper is to identify and summarize the trials that use atezolizumab as a first-line agent in chemotherapy-naïve patients with NSCLC. Methods: A database search was performed on Pubmed, Embase, and Wiley Cochrane Library-Central Register of Controlled Trials to identify clinical trials using atezolizumab as first-line therapy in NSCLC...
2018: Frontiers in Oncology
Xiaofen Li, Xia Li, Xuefeng Fang, Ying Yuan
To date, there is no standard third-line therapy for EGFR - and ALK -negative lung squamous cell carcinoma (SCC). Apatinib, an oral small-molecule VEGFR-2 inhibitor, has shown good therapeutic effect and safety in chemotherapy-refractory gastric cancer, but its efficacy in lung SCC is not determined. In this report, we present a 69-year-old Chinese man with locally advanced EGFR- and ALK-negative lung SCC, who received apatinib after failure of 2 treatment regimens. After 4 months of apatinib therapy, chest computed tomography scan showed a large cavity in the lung tumor, while there was minimal change in tumor size...
2018: OncoTargets and Therapy
Xiaoyan Si, Li Zhang, Hanping Wang, Xiaotong Zhang, Mengzhao Wang, Baohui Han, Kai Li, Qiming Wang, Jianhua Shi, Zhehai Wang, Yin Cheng, Jianxing He, Yuankai Shi, Weiqiang Chen, Xiuwen Wang, Yi Luo, Kejun Nan, Faguang Jin, Baolan Li, Yinlan Chen, Jianying Zhou, Donglin Wang
OBJECTIVES: Anlotinib is a novel multi-target tyrosine Kinase inhibitor that inhibits VEGFR2/3, FGFR1-4, PDGFD α/β, c-Kit and Ret. In the phase III ALTER-0303 trial (Clinical Trial Registry ID: NCT 02388919), anlotinib significantly improved overall survival versus placebo in advanced non-small-cell lung cancer (NSCLC) patients who had received at least two previous chemotherapy and epidermal growth factor receptor/anaplastic lymphoma kinase targeted therapy regimens. This study assessed quality of life (QoL) in these patients...
August 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Fengying Wu, Shijia Zhang, Anwen Xiong, Guanghui Gao, Wei Li, Weijing Cai, Chunxia Su, Xiaoxia Chen, Fei Zhou, Jing Zhao, Shengxiang Ren, Caicun Zhou
OBJECTIVES: Apatinib exhibits broad-spectrum antitumor activities by selectively inhibiting vascular endothelial growth factor receptor-2. This study evaluated the efficacy and safety of apatinib in patients with advanced non-squamous non-small-cell lung cancer who were heavily pretreated or not suitable to receive standard second-line chemotherapy. PATIENTS AND METHODS: This was an open-label, single-arm phase II clinical trial (ClinicalTrials.govNCT02515435). Patients received 500 or 750 mg apatinib daily until progression, unacceptable toxicity, withdrawal, or death...
June 27, 2018: Clinical Lung Cancer
K Patatsos, T M Shekhar, C J Hawkins
Osteosarcoma, a common malignancy in large dog breeds, typically metastasises from long bones to lungs and is usually fatal within 1 to 2 years of diagnosis. Better therapies are needed for canine patients and their human counterparts, a third of whom die within 5 years of diagnosis. We compared the in vitro sensitivity of canine osteosarcoma cells derived from 4 tumours to the currently used chemotherapy drugs doxorubicin and carboplatin, and 4 new anti-cancer drugs. Agents targeting histone deacetylases or PARP were ineffective...
July 12, 2018: Veterinary and Comparative Oncology
Nobuko Matsuura, Genju Koh, Chihiro Konishi, Satoshi Minamino, Yoshinori Takahara, Hiromasa Harada, Ken Kodama, Masanori Emoto
Programmed cell death-1 (PD-1) and programmed cell death-ligand-1 (PD-L1) inhibitors have been highlighted in the field of cancer treatment. The interaction between PD-1 and PD-L1 is thought to play an important role in the regulation of the self-immune tolerance mechanism, so blocking these molecules may cause serious immune-related adverse events (IrAE), including fulminant insulin-dependent (type 1) diabetes. Here, we describe a patient with fulminant type 1 diabetes induced by nivolumab, an anti-PD-1 antibody...
July 11, 2018: Cancer Immunology, Immunotherapy: CII
Cesare Gridelli, Paolo Antonio Ascierto, Francesco Grossi, Editta Baldini, Adolfo Favaretto, Maria Chiara Garassino, Alessandro Morabito, Maria Rita Migliorino, Antonio Rossi, Filippo de Marinis
BACKGROUND: Most patients with advanced non-small cell lung cancer (NSCLC) have a poor prognosis and receive limited benefit from conventional treatments, especially in later lines of therapy. In recent years, several novel therapies have been approved for second- and third-line treatment of advanced NSCLC beyond old chemotherapy agents (docetaxel and pemetrexed) and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI, erlotinib). In particular, the new antiangiogenetics (nindetanib and ramucirumab) in combination with docetaxel and immunotherapy (nivolumab, pembrolizumab and atezolizumab) have been recently approved and represent new treatment options...
July 11, 2018: Current Clinical Pharmacology
Asunción Díaz-Serrano, Pablo Gella, Elisabeth Jiménez, Jon Zugazagoitia, Luis Paz-Ares Rodríguez
Lung cancer is the second most common malignant tumor and the leading cause of cancer death. Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is a distinct subtype of lung cancer comprising approximately 15-40% of non-squamous tumors. The development of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) has been a significant step forward in the treatment of patients with EGFR-mutant tumors, and over the last few years has been the therapy of choice in the initial management of patients with activating mutations in EGFR, with some differences in efficacy and toxicity profile...
June 18, 2018: Drugs
Yoshiaki Tsukizawa, Keisuke Kondo, Toshihisa Ichiba, Hiroshi Naito, Kazuhito Mizuki, Ken Masuda
Nivolumab, a new immune checkpoint inhibitor that has been found to improve outcomes for patients with some advanced cancers, is being increasingly used. Immune checkpoint inhibitors can cause immune-related adverse events, including dermatitis, enterocolitis, hepatitis and hypophysitis, but adrenal insufficiency rarely occurs. We present a case of Nivolumab-induced adrenal insufficiency in a man who complained of refractory hypotension. A 52-year-old man with non-small cell lung cancer visited our emergency department complaining of fatigue and diarrhea...
May 2018: Nagoya Journal of Medical Science
Keke Nie, Zhongfa Zhang, Chunling Zhang, Chuanxin Geng, Ling Zhang, Xiajuan Xu, Shichao Liu, Songping Wang, Xingjun Zhuang, Ketao Lan, Youxin Ji
OBJECTIVE: To compare the efficacy and toxicity of osimertinib versus docetaxel-bevacizumab as third-line treatment in EGFR T790M mutated NSCLC. METHODS: In this phase 3, open-label, three-center study, we randomly assigned (1:1) previously treated with TKI-chemotherapy or chemotherapy-TKI recurrent or metastatic advanced non-squamous lung cancer patients into two groups. These patients had acquired EGFR T790M resistance mutation confirmed by tumor tissues or serum...
July 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Pedro N Aguiar, Benjamin Haaland, Wungki Park, Pui San Tan, Auro Del Giglio, Gilberto de Lima Lopes
Importance: The survival of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations has improved substantially in the last decade with the development of targeted tyrosine kinase inhibitors (TKIs). Osimertinib, a third-generation TKI that is approved by the US Food and Drug Administration for the treatment of patients who develop EGFR T790M mutations, has recently shown improved clinical outcomes compared with gefitinib and erlotinib for treatment-naive patients...
May 31, 2018: JAMA Oncology
Christopher A Bly, Cliff Molife, Jacqueline Brown, Mahesh K Tawney, Gebra Cuyun Carter, Frank N Cinfio, Robert W Klein
BACKGROUND: Necitumumab (Neci) was the first biologic approved by the FDA for use in combination with gemcitabine and cisplatin (Neci + GCis) in first-line treatment of metastatic squamous non-small cell lung cancer (msqNSCLC). The potential financial impact on a health plan of adding Neci + GCis to drug formularies may be important to value-based decision makers in the United States, given ever-tightening budget constraints. OBJECTIVE: To estimate the budget impact of introducing Neci + GCis for first-line treatment of msqNSCLC from U...
June 2018: Journal of Managed Care & Specialty Pharmacy
Si-Qi Feng, Guang-Ji Wang, Jing-Wei Zhang, Yuan Xie, Run-Bin Sun, Fei Fei, Jing-Qiu Huang, Ying Wang, Ji-Ye Aa, Fang Zhou
Apatinib, a small-molecule inhibitor of VEGFR-2, has attracted much attention due to its encouraging anticancer activity in third-line clinical treatment for many malignancies, including non-small cell lung cancer (NSCLC). Its usage in second-line therapy with chemotherapeutic drugs is still under exploration. In this study we investigated the antitumor effect of apatinib combined with docetaxel against NSCLC and its cellular pharmacokinetic basis. A549 xenograft nude mice were treated with apatinib (100 mg/kg every day for 20 days) combined with docetaxel (8 mg/kg, ip, every four days for 5 times)...
May 17, 2018: Acta Pharmacologica Sinica
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
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
Guoyong Han, Long Zhang, Xuhao Ni, Zhiqiang Chen, Xiongxiong Pan, Qin Zhu, Shu Li, Jindao Wu, Xinli Huang, Xuehao Wang
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has the third highest mortality rate among all cancers. MicroRNAs are a class of endogenous, single-stranded short noncoding RNAs. The purpose of this study was to study the role of microRNA-873 in HCC. METHODS: The expression of miRNA-873 and tumor suppressor in lung cancer 1 (TSLC1) in HCC tissues and cell lines was detected by real-time quantitative RT-PCR (RT-qPCR) or western blot...
2018: Cellular Physiology and Biochemistry
T Stockley, C A Souza, P K Cheema, B Melosky, S Kamel-Reid, M S Tsao, A Spatz, A Karsan
Epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are recommended as first-line systemic therapy for patients with non-small-cell lung cancer (nsclc) having mutations in the EGFR gene. Resistance to tkis eventually occurs in all nsclc patients treated with such drugs. In patients with resistance to tkis caused by the EGFR T790M mutation, the third-generation tki osimertinib is now the standard of care. For optimal patient management, accurate EGFR T790M testing is required. A multidisciplinary working group of pathologists, laboratory medicine specialists, medical oncologists, a respirologist, and a thoracic radiologist from across Canada was convened to discuss best practices for EGFR T790M mutation testing in Canada...
April 2018: Current Oncology
Keke Nie, Haiping Jiang, Chunling Zhang, Chuanxin Geng, Xiajuan Xu, Ling Zhang, Hao Zhang, Zhongfa Zhang, Ketao Lan, Youxin Ji
Purpose: To identify the somatic mutated genes for optimal targets of non-small-cell lung cancer after resistance to osimertinib treatment. Patients and Methods: Study patients all had advanced lung adenocarcinoma and acquired resistance to osimertinib as a second- or third-line treatment. These patients had harboring EGFR T790M mutation before osimertinib treatment, which was confirmed by Amplification Refractory Mutation System (ARMS) PCR or Next-Generation Sequencing (NGS)...
2018: BioMed Research International
Hiroaki Akamatsu, Nobuyuki Katakami, Isamu Okamoto, Terufumi Kato, Young Hak Kim, Fumio Imamura, Masaharu Shinkai, Rachel A Hodge, Hirohiko Uchida, Toyoaki Hida
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with EGFR mutant non-small-cell lung cancer (NSCLC). However, most patients become resistant to these drugs, so their disease progresses. Osimertinib, a third-generation EGFR-TKI that can inhibit the kinase even when the common resistance-conferring Thr790Met (T790M) mutation is present, is a promising therapeutic option for patients whose disease has progressed after first-line EGFR-TKI treatment...
June 2018: Cancer Science
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