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document
Ganitumab with either exemestane or fulvestrant for postmenopausal women with advanced , hormone-receptor-positive breast cancer : a randomised , controlled , double-blind , phase 2 trial . BACKGROUND Insulin-like growth factors ( IGF-1 and IGF-2 ) bind to the IGF-1 receptor ( IGF-1R ) , increasing cell proliferation and survival . Ganitumab is a monoclonal IgG1 antibody that blocks IGF-1R . We tested the efficacy and safety of adding ganitumab to endocrine treatment for patients with hormone-receptor-positive breast cancer . METHODS We did this phase 2 trial in outpatient clinics and hospitals . We enrolled postmenopausal women with hormone-receptor-positive , locally advanced or metastatic breast cancer previously treated with endocrine treatment . They were randomly assigned ( 2:1 ) with a central randomisation schedule to receive intravenous ganitumab 12 mg per kg bodyweight or placebo in combination with open-label intramuscular fulvestrant ( 500 mg on day 1 , then 250 mg on days 15 , 29 , and every 28 days ) or oral exemestane ( 25 mg once daily ) on a 28-day cycle . Patients , investigators , study monitors , and the sponsor staff were masked to treatment allocation . Response was assessed every 8 weeks . The primary endpoint was median progression-free survival in the intention-to-treat population . We analysed overall survival as one of our secondary endpoints . The study is registered at ClinicalTrials.gov , number NCT00626106 . FINDINGS We screened 189 patients and enrolled 156 ( 106 in the ganitumab group and 50 in the placebo group ) . Median progression-free survival did not differ significantly between the ganitumab and placebo groups ( 3·9 months , 80 % CI 3·6-5·3 vs 5·7 months , 4·4-7·4 ; hazard ratio [ HR ] 1·17 , 80 % CI 0·91-1·50 ; p=0·44 ) . However , overall survival was worse in the the ganitumab group than in the placebo group ( HR 1·78 , 80 % CI 1·27-2·50 ; p=0·025 ) . With the exception of hyperglycaemia , adverse events were generally similar between groups . The most common grade 3 or higher adverse event was neutropenia-reported by six of 106 ( 6 % ) patients in the ganitumab group and one of 49 ( 2 % ) in the placebo group . Hyperglycaemia was reported by 12 of 106 ( 11 % ) patients in the ganitumab group ( with six patients having grade 3 or 4 hyperglycaemia ) and none of 49 in the placebo group . Serious adverse events were reported by 27 of 106 ( 25 % ) patients in the ganitumab group and nine of 49 ( 18 % ) patients in the placebo group . INTERPRETATION Addition of ganitumab to endocrine treatment in women with previously treated hormone-receptor-positive locally advanced or metastatic breast cancer did not improve outcomes . Our results do not support further study of ganitumab in this subgroup of patients . FUNDING Amgen .
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Intervention_Pharmacological
Ganitumab
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Intervention_Pharmacological
exemestane
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Intervention_Pharmacological
fulvestrant
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Intervention_Pharmacological
Ganitumab
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Intervention_Pharmacological
intravenous ganitumab
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Intervention_Control
placebo
58406
Intervention_Physical
open-label intramuscular fulvestrant
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Intervention_Pharmacological
exemestane
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Intervention_Pharmacological
ganitumab
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Intervention_Pharmacological
ganitumab
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Outcome_Physical
cell proliferation
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Outcome_Mortality
survival
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Outcome_Other
efficacy
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Outcome_Other
safety
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Outcome_Mortality
median progression-free survival
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Outcome_Mortality
overall survival
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Outcome_Mortality
Median progression-free survival