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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
KeywordsMedical sciences
Oncology medical sciences
Radiology and nuclear medicine pharmacy and pharmacology biology
Cytology and histology
Issue Date2012
PublisherAmerican Society of Clinical Oncology. The Journal's web site is located at http://www.jco.org/
Citation
The 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL., 1-5 June 2012. In Journal of Clinical Oncology, 2012, v. 30 n. 15 suppl., abstract 4108 How to Cite?
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. © 2012 by American Society of Clinical Oncology
DescriptionThis journal suppl. contain 2012 ASCO Meeting Abstracts
Open Access Journal
Persistent Identifierhttp://hdl.handle.net/10722/186976
ISSN
2023 Impact Factor: 42.1
2023 SCImago Journal Rankings: 10.639

 

DC FieldValueLanguage
dc.contributor.authorYau, TCCen_US
dc.contributor.authorSukeepaisarnjaroen, Wen_US
dc.contributor.authorChao, Yen_US
dc.contributor.authorYen, CJen_US
dc.contributor.authorLausoontornsiri, Wen_US
dc.contributor.authorChen, PJen_US
dc.contributor.authorSanpajit, Ten_US
dc.contributor.authorLencioni, Ren_US
dc.contributor.authorCamp, ACen_US
dc.contributor.authorCox, DSen_US
dc.contributor.authorKallender, Hen_US
dc.contributor.authorOttesen, LHen_US
dc.contributor.authorPoon, RTPen_US
dc.date.accessioned2013-08-20T12:26:30Z-
dc.date.available2013-08-20T12:26:30Z-
dc.date.issued2012en_US
dc.identifier.citationThe 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL., 1-5 June 2012. In Journal of Clinical Oncology, 2012, v. 30 n. 15 suppl., abstract 4108en_US
dc.identifier.issn0732-183X-
dc.identifier.urihttp://hdl.handle.net/10722/186976-
dc.descriptionThis journal suppl. contain 2012 ASCO Meeting Abstracts-
dc.descriptionOpen Access Journal-
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. © 2012 by American Society of Clinical Oncology-
dc.languageengen_US
dc.publisherAmerican Society of Clinical Oncology. The Journal's web site is located at http://www.jco.org/-
dc.relation.ispartofJournal of Clinical Oncologyen_US
dc.subjectMedical sciences-
dc.subjectOncology medical sciences-
dc.subjectRadiology and nuclear medicine pharmacy and pharmacology biology-
dc.subjectCytology and histology-
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)en_US
dc.typeConference_Paperen_US
dc.identifier.emailYau, TCC: tyaucc@hku.hken_US
dc.identifier.emailPoon, RTP: poontp@hku.hken_US
dc.identifier.authorityYau, TCC=rp01466en_US
dc.identifier.authorityPoon, RTP=rp00446en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1200/jco.2012.30.15_suppl.4108-
dc.identifier.hkuros217114en_US
dc.identifier.hkuros202728-
dc.identifier.volume30en_US
dc.identifier.issue15 suppl.en_US
dc.publisher.placeUnited States-
dc.identifier.issnl0732-183X-

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