Canadian Cancer Trials Group IND197: a phase II study of foretinib in patients with estrogen receptor, progesterone receptor, and human ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-05

AUTHORS

Daniel Rayson, Sasha Lupichuk, Kylea Potvin, Susan Dent, Tamara Shenkier, Sukhbinder Dhesy-Thind, Susan L. Ellard, Catherine Prady, Muhammad Salim, Patricia Farmer, Ghasson Allo, Ming-Sound Tsao, Alison Allan, Olga Ludkovski, Maria Bonomi, Dongsheng Tu, Linda Hagerman, Rachel Goodwin, Elizabeth Eisenhauer, Penelope Bradbury

ABSTRACT

In murine models, overexpression of the MET receptor transgene induces tumors with human basal gene expression characteristics supporting MET inhibition as a treatment strategy for triple-negative breast cancer (TNBC). Foretinib is an oral multi-kinase inhibitor of MET, RON, AXL, TIE-2, and VEGF receptors with anti-tumor activity in advanced HCC and papillary renal cell cancer. Patients with centrally reviewed primary TNBC and 0-1 prior regimens for metastatic disease received daily foretinib 60 mg po in a 2-stage single-arm trial. Primary endpoints were objective response and early progression rates per RECIST 1.1. In stage 2, correlative studies of MET, PTEN, EGFR, and p53 on archival and fresh tumor specimens were performed along with enumeration of CTCs. 45 patients were enrolled with 37 patients having response evaluable and centrally confirmed primary TNBC (cTNBC). There were 2 partial responses (ITT 4.7 % response evaluable cTNBC 5.4 %) with a median duration of 4.4 months (range 3.7-5 m) and 15 patients had stable disease (ITT 33 %, response evaluable cTNBC 40.5 %) with a median duration of 5.4 months (range 2.3-9.7 m). The most common toxicities (all grades/grade 3) were nausea (64/4 %), fatigue (60/4 %), hypertension (58/49 %), and diarrhea (40/7 %). Six serious adverse events were considered possibly related to foretinib and 4 patients went off study due to adverse events. There was no correlation between MET positivity and response nor between response and PTEN, EGFR, p53, or MET expression in CTCs. Although CCTG IND 197 did not meet its primary endpoint, the observation of a clinical benefit rate of 46 % in this cTNBC population suggests that foretinib may have clinical activity as a single, non-cytotoxic agent in TNBC (ClinicalTrials.gov number, NCT01147484). More... »

PAGES

109-116

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10549-016-3812-1

DOI

http://dx.doi.org/10.1007/s10549-016-3812-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033072492

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27116183


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    "description": "In murine models, overexpression of the MET receptor transgene induces tumors with human basal gene expression characteristics supporting MET inhibition as a treatment strategy for triple-negative breast cancer (TNBC). Foretinib is an oral multi-kinase inhibitor of MET, RON, AXL, TIE-2, and VEGF receptors with anti-tumor activity in advanced HCC and papillary renal cell cancer. Patients with centrally reviewed primary TNBC and 0-1 prior regimens for metastatic disease received daily\u00a0foretinib 60\u00a0mg po in a 2-stage single-arm trial. Primary endpoints were objective response and early progression rates per RECIST 1.1. In stage 2, correlative studies of MET, PTEN, EGFR, and p53 on archival and fresh tumor specimens were performed along with enumeration of CTCs. 45 patients were enrolled with 37 patients having response evaluable and centrally confirmed primary TNBC (cTNBC). There were 2 partial responses (ITT 4.7\u00a0% response evaluable cTNBC 5.4\u00a0%) with a median duration of 4.4\u00a0months (range 3.7-5\u00a0m) and 15 patients had stable disease (ITT 33\u00a0%, response evaluable cTNBC 40.5\u00a0%) with a median duration of 5.4\u00a0months (range 2.3-9.7\u00a0m). The most common toxicities (all grades/grade 3) were nausea (64/4\u00a0%), fatigue (60/4\u00a0%), hypertension (58/49\u00a0%), and diarrhea (40/7\u00a0%). Six serious adverse events were considered possibly related to foretinib and 4 patients went off study due to adverse events. There was no correlation between MET positivity and response nor between response and PTEN, EGFR, p53, or MET expression in CTCs. Although CCTG IND 197 did not meet its primary endpoint, the observation of a clinical benefit rate of 46\u00a0% in this cTNBC population suggests that foretinib may have clinical activity as a single, non-cytotoxic agent in TNBC (ClinicalTrials.gov number, NCT01147484).", 
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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s10549-016-3812-1'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s10549-016-3812-1'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s10549-016-3812-1'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s10549-016-3812-1'


 

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