Predictive biomarkers for targeting insulin-like growth factor-I (IGF-I) receptor

Carden, Craig P.; Molife, L Rhoda; Bono, Johann S. de

doi:10.1158/1535-7163.mct-09-0641

Cited by 13 publications

(9 citation statements)

References 14 publications

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“…These preliminary data and those already published on the potential application of CTCs expressing IGF-IR (de Bono et al , 2007) support the ongoing analysis of PD end points, with a view to identifying predictive biomarkers of response to this and other agents in this class of drugs (Carden et al , 2009). In this study, IGF-IR+ CTCs were detected in all patients with ⩾5 CTCs per 7.5 ml at enrolment (de Bono et al , 2007).…”

Section: Discussionsupporting

confidence: 65%

The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study

et al. 2010

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Background:This phase Ib trial assessed safety, tolerability, and maximum tolerated dose (MTD) of figitumumab (CP-751,871), a fully human monoclonal antibody targeting the insulin-like growth factor type 1 receptor (IGF-IR), in combination with docetaxel.Methods:Patients with advanced solid tumours were treated with escalating dose levels of figitumumab plus 75 mg m–2 docetaxel every 21 days. Safety, efficacy, pharmacokinetics (PKs), and biomarker responses were evaluated.Results:In 46 patients, no dose-limiting toxicities were attributable to the treatment combination. Grade 3 and 4 toxicities included neutropaenia (n=28), febrile neutropaenia (n=11), fatigue (n=10), leukopaenia (n=7), diarrhoea (n=5), hyperglycaemia, lymphopaenia, cellulitis, DVT, and pain (all n=1). The MTD was not reached. Four partial responses were observed; 12 patients had disease stabilisation of ⩾6 months. Pharmacokinetic and biomarker analyses showed a dose-dependent increase in plasma exposure, and complete sIGF-IR downregulation at doses of ⩾3 mg kg–1. Pharmacokinetics of docetaxel in combination was similar to when given alone. Out of 18 castration-resistant prostate cancer patients, 10 (56%) had ⩾5 circulating tumour cells (CTCs) per 7.5 ml of blood at baseline: 6 out of 10 (60%) had a decline from ⩾5 to <5 CTCs and 9 out of 10 (90%) had a ⩾30% decline in CTCs after therapy.Conclusions:Figitumumab and docetaxel in combination are well tolerated. Further evaluation is warranted.

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Section: Discussionsupporting

confidence: 65%

The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study

et al. 2010

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“…However, clinical benefit with targeted agents in other sarcoma subtypes has been elusive 22. Targeted therapies can produce dramatic tumour shrinkage when cancer-cell survival is dependent on the target’s expression or activation, but the expression of a target does not necessarily correlate with response to its inhibition 23. IGF-1R is widely expressed and implicated as having a key role in several sarcoma subtypes, including Ewing’s sarcoma and rhabdomyosarcoma 11.…”

Section: Discussionmentioning

confidence: 99%

Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma: a phase 1 expansion cohort study

Olmos¹,

Postel-Vinay²,

Molife³

et al. 2010

The Lancet Oncology

304

190

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“…It is also tempting to speculate that other tumor types with dysregulation of the pathway, for instance colorectal and ovarian cancer, which show loss of imprinting at the IGF-2 locus, might also constitute indications with dependence on the pathway and increased likelihood of benefit. Predictive biomarkers of response to IGF-1R targeting agents is a pressing issue (50), and a variety of preclinical studies have suggested that expression or phosphorylation of IGF-1R, levels of the ligands IGF-1 and 2, and levels of the IGFBPs and the adaptor proteins IRS-1 and IRS-2 may have predictive value in identifying responsive patients (4,(51)(52)(53)(54). Gene expression signatures predictive of response to some IGF-1R targeting agents have also been described (31,54).…”

Section: Future Directionsmentioning

confidence: 99%

Targeting the Insulin-like Growth Factor Receptor-1R Pathway for Cancer Therapy

Zha¹,

Lackner²

2010

Clinical Cancer Research

128

111

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Signaling through the insulin-like growth factor receptor (IGF-1R) is required for neoplastic transformation by a number of oncogenes, and preclinical validation studies have suggested IGF-1R is an attractive target for anticancer therapy. A number of small molecules and antibodies targeting IGF-1R have entered clinical development, and early results have suggested that these agents have generally acceptable safety profiles as single agents. Some evidence of antitumor activity has also been reported. This review highlights key aspects of the IGF-1R signaling pathway that implicate it as an attractive therapeutic target in the management of cancer, as well as some key lessons that have emerged from early clinical development of anti-IGF-1R targeting agents. In addition, we consider the importance of selecting indications characterized by pathological alterations in the signaling pathway, rational selection of combinations based on signaling pathway interactions, and strategies for patient selection based on analysis of predictive biomarkers. Clin Cancer Res; 16(9); 2512-7. ©2010 AACR.

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Predictive biomarkers for targeting insulin-like growth factor-I (IGF-I) receptor

Cited by 13 publications

References 14 publications

The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study

The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study

Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma: a phase 1 expansion cohort study

Targeting the Insulin-like Growth Factor Receptor-1R Pathway for Cancer Therapy

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