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Conference Paper: A phase I/II study of Foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2 and VEGFR in advanced hepatocellular carcinoma (HCC)

TitleA phase I/II study of Foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2 and VEGFR in advanced hepatocellular carcinoma (HCC)
Authors
Issue Date2012
PublisherAmerican Society of Clinical Oncology. The Journal's web site is located at http://www.jco.org/
Citation
2012 Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, 1-5 June 2012. In Journal of Clinical Oncology, 2012, v. 30 n. 15 Suppl, p. Abstract no.4108 How to Cite?
Abstract
Background: Hepatocyte growth factor (HGF)/MET signalling plays a pivotal role in tumor cell proliferation, migration and invasion in HCC and circulating levels of HGF correlate with poor prognosis. This phase I/II trial (MET111645) evaluated foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2 and VEGFR, as first-line therapy in Asian advanced-HCC patients. Methods: Asian patients with measurable, unresectable/metastatic HCC, no prior sorafenib or other multi-kinase inhibitors, ECOG PS 0-1, adequate organ function and Child-Pugh grade A were recruited. The phase I was a standard 3+3 dose escalation design with a phase II cohort expansion. The primary endpoint was safety and tolerability at the maximum tolerated dose (MTD) and the secondary endpoints included antitumor activity (objective response rate [ORR], disease stabilization rate [DSR; confirmed CR/PR or SD for at least 12 weeks], and time to progression [TTP] evaluated by central review according to modified RECIST), and overall survival (OS) at the MTD, plus pharmacokinetics (PK). Results: Thirteen patients were enrolled in phase I. Two dose-limiting toxicities (DLT) (renal failure, proteinuria) were observed at 45 mg once daily (QD) but no DLTs were observed at 30 mg QD. Thus, the MTD was determined to be 30 mg QD. A further 32 patients were enrolled at the MTD, for a study total of 39 patients treated at 30 mg QD. The most common AEs, independent of causality,were hypertension (36%), decreased appetite (23%), and pyrexia (21%). The most common SAEs were hepatic encephalopathy (10%) and ascites (8%). Two patients discontinued foretinib due to AEs. No dose reductions were reported. Thirty-eight patients were evaluable for efficacy. The ORR was 24% (95% CI 11-40), DSR 79% (95% CI; 63-90), and the median TTP was 4.2 months (95% CI 2.7-7.5). Mature OS data will be presented. Mean steady-state exposures (AUC/Cmax) were comparable after administration of foretinib at 30 and 45 mg. Conclusions: Foretinib has an acceptable safety, tolerability, and PK profile in an Asian HCC population. It has demonstrated promising antitumor activity that warrants further testing in a randomized setting.
Persistent Identifierhttp://hdl.handle.net/10722/160425
ISSN
2013 Impact Factor: 17.879

 

DC FieldValueLanguage
dc.contributor.authorYau, TCC-
dc.contributor.authorSukeepaisarnjaroen, W-
dc.contributor.authorChao, Y-
dc.contributor.authorYen, CJ-
dc.contributor.authorLausoontornsiri, W-
dc.contributor.authorChen, PJ-
dc.contributor.authorSanpajit, T-
dc.contributor.authorLencioni, R-
dc.contributor.authorCamp, AC-
dc.contributor.authorCox, DS-
dc.contributor.authorKallender, H-
dc.contributor.authorOttesen, LH-
dc.contributor.authorPoon, RTP-
dc.date.accessioned2012-08-16T06:11:05Z-
dc.date.available2012-08-16T06:11:05Z-
dc.date.issued2012-
dc.identifier.citation2012 Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, 1-5 June 2012. In Journal of Clinical Oncology, 2012, v. 30 n. 15 Suppl, p. Abstract no.4108-
dc.identifier.issn0732-183X-
dc.identifier.urihttp://hdl.handle.net/10722/160425-
dc.description.abstractBackground: Hepatocyte growth factor (HGF)/MET signalling plays a pivotal role in tumor cell proliferation, migration and invasion in HCC and circulating levels of HGF correlate with poor prognosis. This phase I/II trial (MET111645) evaluated foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2 and VEGFR, as first-line therapy in Asian advanced-HCC patients. Methods: Asian patients with measurable, unresectable/metastatic HCC, no prior sorafenib or other multi-kinase inhibitors, ECOG PS 0-1, adequate organ function and Child-Pugh grade A were recruited. The phase I was a standard 3+3 dose escalation design with a phase II cohort expansion. The primary endpoint was safety and tolerability at the maximum tolerated dose (MTD) and the secondary endpoints included antitumor activity (objective response rate [ORR], disease stabilization rate [DSR; confirmed CR/PR or SD for at least 12 weeks], and time to progression [TTP] evaluated by central review according to modified RECIST), and overall survival (OS) at the MTD, plus pharmacokinetics (PK). Results: Thirteen patients were enrolled in phase I. Two dose-limiting toxicities (DLT) (renal failure, proteinuria) were observed at 45 mg once daily (QD) but no DLTs were observed at 30 mg QD. Thus, the MTD was determined to be 30 mg QD. A further 32 patients were enrolled at the MTD, for a study total of 39 patients treated at 30 mg QD. The most common AEs, independent of causality,were hypertension (36%), decreased appetite (23%), and pyrexia (21%). The most common SAEs were hepatic encephalopathy (10%) and ascites (8%). Two patients discontinued foretinib due to AEs. No dose reductions were reported. Thirty-eight patients were evaluable for efficacy. The ORR was 24% (95% CI 11-40), DSR 79% (95% CI; 63-90), and the median TTP was 4.2 months (95% CI 2.7-7.5). Mature OS data will be presented. Mean steady-state exposures (AUC/Cmax) were comparable after administration of foretinib at 30 and 45 mg. Conclusions: Foretinib has an acceptable safety, tolerability, and PK profile in an Asian HCC population. It has demonstrated promising antitumor activity that warrants further testing in a randomized setting.-
dc.languageeng-
dc.publisherAmerican Society of Clinical Oncology. The Journal's web site is located at http://www.jco.org/-
dc.relation.ispartofJournal of Clinical Oncology-
dc.titleA phase I/II study of Foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2 and VEGFR in advanced hepatocellular carcinoma (HCC)-
dc.typeConference_Paper-
dc.identifier.emailYau, TCC: tyaucc@hku.hk-
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hk-
dc.identifier.authorityYau, TCC=rp01466-
dc.identifier.authorityPoon, RTP=rp00446-
dc.identifier.hkuros202728-
dc.identifier.volume30-
dc.identifier.issue15 Suppl-
dc.identifier.spageAbstract no.4108-
dc.identifier.epageAbstract no.4108-
dc.publisher.placeUnited States-

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