Abstract：
BACKGROUND:The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are associated with increases in janus kinase 2 (JAK2) signaling, often resulting from the JAK2 V617F mutation. LY2784544 (gandotinib) is a potent, selective, small-molecule inhibitor of JAK2 that has potential dose-dependent selectivity for the JAK2 V617F mutation and may inhibit additional JAK2 mutant isoforms in nonclinical testing. METHODS:A multicenter, single-arm, outpatient phase 2 study evaluated the efficacy, safety, and pharmacokinetics (PK) of gandotinib administered to patients (120 mg once daily) with MPNs, including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). Between May 2012 and March 2015, 138 patients received at least one dose of study drug. FINDINGS:Most frequent Grade 3 or 4 treatment-emergent adverse events that were considered study-drug related were anemia (11.6%), hyperuricemia (3.2%), fatigue (2.9%), diarrhea (2.2%), and thrombocytopenia (2.2%). Overall response rates (ORRs) in patients with JAK2 V617F-mutated PV, ET, and MF were 95%, 90.5%, and 9.1%, respectively, while patients with ET and MF without the JAK2 V617F mutations had ORRs of 43.7% and 0%, respectively. INTERPRETATIONS:LY2784544 demonstrated efficacy in JAK2 V617F-mutated MPNs, including in patients previously on ruxolitinib therapy, who had an ORR of 3.3%. At the 1-year visit, 44% of patients experienced a ≥50% improvement in the MPN-Symptom Assessment Form Total Symptom Score, and 26% of patients had a 50% reduction in Brief Fatigue Inventory score.
journal_name
Leuk Resjournal_title
Leukemia researchauthors
Berdeja J,Palandri F,Baer MR,Quick D,Kiladjian JJ,Martinelli G,Verma A,Hamid O,Walgren R,Pitou C,Li PL,Gerds ATdoi
10.1016/j.leukres.2018.06.014subject
Has Abstractpub_date
2018-08-01 00:00:00pages
82-88eissn
0145-2126issn
1873-5835pii
S0145-2126(18)30137-1journal_volume
71pub_type
杂志文章,多中心研究abstract：:p23 is a heat shock protein 90 (Hsp90) cochaperone that plays a significant role in estrogen receptor (ER) alpha signal transduction and telomerase activity; it is up-regulated in several cancers. Recent studies have found that high level of p23 may promote tumor progression and poor prognosis in breast cancer patient...
journal_title：Leukemia research
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doi：10.1016/0145-2126(86)90344-9
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journal_title：Leukemia research
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pub_type： 杂志文章
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journal_title：Leukemia research
pub_type： 临床试验,杂志文章,多中心研究
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更新日期：2007-05-01 00:00:00
