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Alectinib

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https://www.readbyqxmd.com/read/28646771/efficacy-of-alectinib-in-central-nervous-system-metastases-in-crizotinib-resistant-alk-positive-non-small-cell-lung-cancer-comparison-of-recist-1-1-and-rano-hgg-criteria
#1
Leena Gandhi, Sai-Hong Ignatius Ou, Alice T Shaw, Fabrice Barlesi, Anne-Marie C Dingemans, Dong-Wan Kim, D Ross Camidge, Brett G M Hughes, James C-H Yang, Javier de Castro, Lucio Crino, Hervé Léna, Pascal Do, Sophie Golding, Walter Bordogna, Ali Zeaiter, Ahmed Kotb, Shirish Gadgeel
BACKGROUND: Central nervous system (CNS) progression is common in patients with anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) receiving crizotinib. Next-generation ALK inhibitors have shown activity against CNS metastases, but accurate assessment of response and progression is vital. Data from two phase II studies in crizotinib-refractory ALK+ NSCLC were pooled to examine the CNS efficacy of alectinib, a CNS-active ALK inhibitor, using Response Evaluation Criteria in Solid Tumours (RECIST version 1...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28625556/alectinib-surpasses-crizotinib-for-untreated-alk-positive-nsclc
#2
Judith A Gilbert
No abstract text is available yet for this article.
June 15, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28606126/pooled-safety-analyses-of-alk-tki-inhibitor-in-alk-positive-nsclc
#3
Qian Zhu, Hao Hu, De-Sheng Weng, Xiao-Fei Zhang, Chang-Long Chen, Zi-Qi Zhou, Yan Tang, Jian-Chuan Xia
BACKGROUND: The anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have been administered to patients with ALK-positive non-small cell lung cancer for a long period of time and show a promising response. However, the differences in the toxicity profiles among these drugs are still unclear. METHODS: We performed a comprehensive search of the MEDLINE, EMBASE, WEB OF SCIENCE and COCHRANE databases from the drugs' inception to May 2016 to identify clinical trials...
June 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28600466/alectinib-superior-to-crizotinib-for-alk-nsclc
#4
(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/28588841/nasogastric-tube-administered-alectinib-achieved-long-term-survival-in-a-crizotinib-refractory-nonsmall-cell-lung-cancer-patient-with-a-poor-performance-status
#5
Osamu Kanai, Young Hak Kim, Koichi Nakatani, Kohei Fujita, Tadashi Mio
Alectinib shows remarkable efficacy against anaplastic lymphoma kinase (ALK)-positive nonsmall cell lung cancer (NSCLC), with minimal adverse effects. Therefore, alectinib may provide a survival benefit to ALK-positive NSCLC patients with a poor performance status. If the medication cannot be taken by mouth, the patient may be given alectinib through a nasogastric tube.
June 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28586279/alectinib-versus-crizotinib-in-untreated-alk-positive-non-small-cell-lung-cancer
#6
Solange Peters, D Ross Camidge, Alice T Shaw, Shirish Gadgeel, Jin S Ahn, Dong-Wan Kim, Sai-Hong I Ou, Maurice Pérol, Rafal Dziadziuszko, Rafael Rosell, Ali Zeaiter, Emmanuel Mitry, Sophie Golding, Bogdana Balas, Johannes Noe, Peter N Morcos, Tony Mok
Background Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease. Methods In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily)...
June 6, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28578501/monitoring-for-and-characterizing-crizotinib-progression-a-chart-review-of-alk-positive-non-small-cell-lung-cancer-patients
#7
Edmond Bendaly, Anand A Dalal, Kenneth Culver, Philip Galebach, Iryna Bocharova, Rebekah Foster, Medha Sasane, Alexander R Macalalad, Annie Guérin
INTRODUCTION: Crizotinib is recommended as first-line therapy for ALK-positive non-small cell lung cancer (NSCLC), but within a year of treatment initiation many patients develop resistance. With the recent approval of second-generation ALK inhibitors, this study assessed how physicians monitor for and diagnose progression and how they alter treatment following progression on crizotinib. METHODS: A panel of oncologists from the United States were surveyed regarding their monitoring practices and criteria for diagnosing progression on crizotinib...
June 3, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28575860/in-vitro-and-in-vivo-anti-tumor-activity-of-alectinib-in-tumor-cells-with-ncoa4-ret
#8
Sachiko Arai, Kenji Kita, Azusa Tanimoto, Shinji Takeuchi, Koji Fukuda, Hiroshi Sato, Seiji Yano
Rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) accounts for approximately 1-2% of all NSCLCs. To date, RET fusions that involve at least six fusion partners in NSCLC, such as KIF5B, CCDC6, NCOA4, TRIM33, CLIP1, and ERC1, have been identified. Recent clinical trials for RET fusion-positive NSCLC using vandetanib or cabozantinib demonstrated positive clinical response and considerable differential activities for RET inhibitors among fusion partners. Alectinib, an approved ALK inhibitor, is reported to inhibit KIF5B-RET and CCDC6-RET...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28559820/nivolumab-therapy-for-synchronous-alk-positive-lung-cancer-and-gastric-cancer
#9
Masahiro Yamasaki, Naomi Saito, Yu Hada, Sayaka Miyamoto, Hideharu Okanobu, Naoya Ikeda, Wakako Daido, Sayaka Ishiyama, Naoko Deguchi, Masaya Taniwaki, Nobuyuki Ohashi
Nivolumab is an immune checkpoint inhibitor with demonstrated efficacy against several malignant tumors. Alterations in driver oncogenes such as EGFR and ALK are a poor prognostic factor in nivolumab therapy for non-small cell lung cancer (NSCLC), whereas a smoking history is a well-known, favorable prognostic factor. However, an efficacy of nivolumab therapy for multiple primary malignant tumors (MPMTs) has not been reported, and its efficacy for driver oncogene-positive NSCLC in smokers is unclear. Herein, we report the case of a patient with a history of heavy smoking who developed synchronous ALK-positive NSCLC and gastric cancer that responded to nivolumab therapy...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28558851/-new-biopsy-at-lung-cancer-progression-rational-treatment-of-resistant-lung-cancer
#10
L B M Hijmering-Kappelle, A J van der Wekken, T J N Hiltermann, H J M Groen
Nowadays, patients with advanced non-small cell lung cancer harbouring a driver mutation undergo targeted treatment. This results in profound tumour responses but inevitably induces resistance after approximately 9 to 12 months. In this article we consider the importance and clinical implications of taking new biopsies to retrieve information regarding resistance mechanisms. There is a shift in the use of other modalities such as radiotherapy and surgery in patients with oligometastatic disease, producing long-lasting responses...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28501140/alectinib-versus-crizotinib-in-patients-with-alk-positive-non-small-cell-lung-cancer-j-alex-an-open-label-randomised-phase-3-trial
#11
Toyoaki Hida, Hiroshi Nokihara, Masashi Kondo, Young Hak Kim, Koichi Azuma, Takashi Seto, Yuichi Takiguchi, Makoto Nishio, Hiroshige Yoshioka, Fumio Imamura, Katsuyuki Hotta, Satoshi Watanabe, Koichi Goto, Miyako Satouchi, Toshiyuki Kozuki, Takehito Shukuya, Kazuhiko Nakagawa, Tetsuya Mitsudomi, Nobuyuki Yamamoto, Takashi Asakawa, Ryoichi Asabe, Tomohiro Tanaka, Tomohide Tamura
BACKGROUND: Alectinib, a potent, highly selective, CNS-active inhibitor of anaplastic lymphoma kinase (ALK), showed promising efficacy and tolerability in the single-arm phase 1/2 AF-001JP trial in Japanese patients with ALK-positive non-small-cell lung cancer. Given those promising results, we did a phase 3 trial to directly compare the efficacy and safety of alectinib and crizotinib. METHODS: J-ALEX was a randomised, open-label, phase 3 trial that recruited ALK inhibitor-naive Japanese patients with ALK-positive non-small-cell lung cancer, who were chemotherapy-naive or had received one previous chemotherapy regimen, from 41 study sites in Japan...
May 10, 2017: Lancet
https://www.readbyqxmd.com/read/28501139/j-alex-alectinib-versus-crizotinib-in-alk-positive-lung-cancer
#12
Justin F Gainor, Alice T Shaw
No abstract text is available yet for this article.
May 10, 2017: Lancet
https://www.readbyqxmd.com/read/28480209/alk-on-my-mind-alectinib-takes-an-early-lead-in-managing-intracranial-disease-in-non-small-cell-lung-cancer-with-alk-rearrangements
#13
EDITORIAL
Phu N Tran, Samuel J Klempner
No abstract text is available yet for this article.
April 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28463570/anaplastic-lymphoma-kinase-inhibitors-in-phase-i-and-phase-ii-clinical-trials-for-non-small-cell-lung-cancer
#14
REVIEW
Niki Karachaliou, Mariacarmela Santarpia, Maria Gonzalez Cao, Cristina Teixido, Aaron E Sosa, Jordi Berenguer, Alejandra Rodriguez Capote, Giuseppe Altavilla, Rafael Rosell
Crizotinib is a first-in-class ALK tyrosine kinase inhibitor (TKI), which has proven its superiority over standard platinum-based chemotherapy for the first-line therapy of ALK-rearranged non-small cell lung cancer (NSCLC) patients. The development of acquired resistance to crizotinib represents an ongoing challenge with the central nervous system being one of the most common sites of relapse. Ceritinib and alectinib are approved second-generation ALK TKIs. Several novel ALK inhibitors, more potent and with different selectivity compared to crizotinib, are currently in development...
June 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28455243/the-second-generation-alk-inhibitor-alectinib-effectively-induces-apoptosis-in-human-neuroblastoma-cells-and-inhibits-tumor-growth-in-a-th-mycn-transgenic-neuroblastoma-mouse-model
#15
Jiaxiong Lu, Shan Guan, Yanling Zhao, Yang Yu, Sarah E Woodfield, Huiyuan Zhang, Kristine L Yang, Shayahati Bieerkehazhi, Lin Qi, Xiaonan Li, Jerry Gu, Xin Xu, Jingling Jin, Jodi A Muscal, Tianshu Yang, Guo-Tong Xu, Jianhua Yang
Activating germline mutations of anaplastic lymphoma kinase (ALK) occur in most cases of hereditary neuroblastoma (NB) and the constitutively active kinase activity of ALK promotes cell proliferation and survival in NB. Therefore, ALK kinase is a potential therapeutic target for NB. In this study, we show that the novel ALK inhibitor alectinib effectively suppressed cell proliferation and induces apoptosis in NB cell lines with either wild-type ALK or mutated ALK (F1174L and D1091N) by blocking ALK-mediated PI3K/Akt/mTOR signaling...
April 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28447912/targeting-ret-in-patients-with-ret-rearranged-lung-cancers-results-from-the-global-multicenter-ret-registry
#16
Oliver Gautschi, Julie Milia, Thomas Filleron, Juergen Wolf, David P Carbone, Dwight Owen, Ross Camidge, Vignhesh Narayanan, Robert C Doebele, Benjamin Besse, Jordi Remon-Masip, Pasi A Janne, Mark M Awad, Nir Peled, Chul-Cho Byoung, Daniel D Karp, Michael Van Den Heuvel, Heather A Wakelee, Joel W Neal, Tony S K Mok, James C H Yang, Sai-Hong Ignatius Ou, Georg Pall, Patrizia Froesch, Gérard Zalcman, David R Gandara, Jonathan W Riess, Vamsidhar Velcheti, Kristin Zeidler, Joachim Diebold, Martin Früh, Sebastian Michels, Isabelle Monnet, Sanjay Popat, Rafael Rosell, Niki Karachaliou, Sacha I Rothschild, Jin-Yuan Shih, Arne Warth, Thomas Muley, Florian Cabillic, Julien Mazières, Alexander Drilon
Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement...
May 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28427013/the-accelerated-path-of-ceritinib-translating-pre-clinical-development-into-clinical-efficacy
#17
REVIEW
Tony S K Mok, Lucio Crino, Enriqueta Felip, Ravi Salgia, Tommaso De Pas, Daniel S W Tan, Laura Q M Chow
The discovery of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) in 2007 led to the development and subsequent approval of the ALK inhibitor crizotinib in 2011. However, despite its clinical efficacy, resistance to crizotinib invariably develops. There is now a next generation of ALK inhibitors, including two that have been approved-ceritinib and alectinib-and others that are in development-brigatinib, lorlatinib and X-396. Ceritinib and the other next-generation ALK inhibitors are more potent than crizotinib and can overcome tumor cell resistance mechanisms...
March 30, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28332433/the-cost-effectiveness-of-alectinib-in-anaplastic-lymphoma-kinase-positive-alk-advanced-nsclc-previously-treated-with-crizotinib
#18
J J Carlson, W Canestaro, A Ravelo, W Wong
Introduction Anaplastic lymphoma kinase (ALK) targeting drugs provide an important option for advanced non-small cell lung cancer patients with this distinct tumor type; however, there is considerable uncertainty as to which drug provides the optimal value after crizotinib treatment. This study estimated the cost-utility of alectinib vs ceritinib from a US payer perspective. Methods A cost-utility model was developed using partition survival methods and three health states: progression-free (PF), post-progression (PP), and death...
July 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28303028/alectinib-ch5424802-antagonizes-abcb1-and-abcg2-mediated-multidrug-resistance-in-vitro-in-vivo-and-ex-vivo
#19
Ke Yang, Yifan Chen, Kenneth Kin Wah To, Fang Wang, Delan Li, Likun Chen, Liwu Fu
Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo...
March 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28296581/three-year-follow-up-of-an-alectinib-phase-i-ii-study-in-alk-positive-non-small-cell-lung-cancer-af-001jp
#20
Tomohide Tamura, Katsuyuki Kiura, Takashi Seto, Kazuhiko Nakagawa, Makoto Maemondo, Akira Inoue, Toyoaki Hida, Hiroshige Yoshioka, Masao Harada, Yuichiro Ohe, Naoyuki Nogami, Haruyasu Murakami, Hiroshi Kuriki, Tadashi Shimada, Tomohiro Tanaka, Kengo Takeuchi, Makoto Nishio
Purpose Alectinib is an anaplastic lymphoma kinase (ALK) -specific kinase inhibitor that seems to be effective against non-small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Patients and Methods Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor-naïve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy...
May 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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