國家衛生研究院 NHRI:Item 3990099045/9899

NHRI > National Institute of Cancer Research > Nai-Jung Chiang > Conference Papers/Meeting Abstract > Item 3990099045/9899

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Title:	Results of Phase II trial of AUY922, a novel heat shock protein inhibitor in patients with metastatic gastrointestinal stromal tumor (GIST) and imatinib and sunitinib therapy
Authors:	Chiang, NJ;Yeh, KH;Chiu, CF;Chen, JS;Yen, CC;Lee, KD;Lin, YL;Bai, LY;Chen, MH;Lin, JS;Yang, Y;Rau, KM;Hsiao, HH;Shan, YS;Chen, LT
Contributors:	National Institute of Cancer Research
Abstract:	Background: Our preclinical studies showed that AUY922 treatment could induce downregulation of KIT protein and apoptosis in both imatinib-sensitive and -resistant GIST cells (Autophagy 2013). This prospective, phase II trial evaluated the efficacy and safety of AUY922 in patients with metastatic GISTs after failure or intolerance to imatinib and sunitinib in an Asian population. Methods: Based on the MTD defined in previous phase I study, infusion 70 mg/m2 of AUY922 was given once weekly, 4 weeks as a cycle. The primary endpoint was disease control rate (DCR, objective response + stable disease ≥ 16 weeks), assessed by computed tomography (CT) scan according to RECIST v1.1 every 8 weeks. Metabolic response was assessed by positron emission tomography (PET)-CT scans performed at baseline and after 4 weeks of treatment. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of informed consent. Results: Between 2011.10 and 2015.01, 25 evaluable patients were enrolled. DCR at 16 weeks was 20% but none had partial response. According to the EORTC-defined PET response criteria, ten patients (40%) had metabolic partial response ( > 25% decrease of SUV from baseline) at 4 weeks after AUY922 treatment. At a median follow-up time of 7.8 months (range, 2.0-33.4 months), median progression-free survival (PFS) was 2.4 months (95% confidence interval (CI), 1.6-3.2 months) and median overall survival was 9.6 months (95% CI, 0-21.1 months). Metabolic partial responders had a trend of better PFS (3.8 vs. 1.9 months in non-responders, P = 0.09). The common adverse events (AEs) were fatigue (82%), visual disturbances (70%), diarrhea (55%). Grade 3/4 AEs included visual field darkening (3.7%), blurred vision (7.4%) and diarrhea (7.4%). Treatment interruption and dose modification were frequently required (62%) in patients with more than 8 weeks of treatment because of grade 2-3 visual field darkening. Conclusions: AUY922 showed modest antitumor activity in heavily pretreated GIST patients. Clinical relevant ocular toxicity was unexpectedly high in current study cohort; its correlation with PK will be further explored.
Date:	2016-02
Relation:	Journal of Clinical Oncology. 2016 Feb;34(4, Suppl.):Meeting Abstract 134.
Link to:	http://meeting.ascopubs.org/cgi/content/abstract/34/4_suppl/134?sid=2fb0fef2-bdd2-429a-a7d9-c43b1a239d2a
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0732-183X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000378109600130
Appears in Collections:	[Nai-Jung Chiang] Conference Papers/Meeting Abstract [Li-Tzong Chen] Conference Papers/Meeting Abstract [Kuan-Te Li(1997-2004)] Conference Papers/Meeting Abstract

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