Ganitumab with either exemestane or fulvestrant for postmenopausal women with
advanced, hormone-receptor-positive breast cancer: a randomised, controlled,
double-blind, phase 2 trial.
Author(s): Robertson JF(1), Ferrero JM, Bourgeois H, Kennecke H, de Boer RH, Jacot W,
McGreivy J, Suzuki S, Zhu M, McCaffery I, Loh E, Gansert JL, Kaufman PA.
Affiliation(s): Author information:
(1)Royal Derby Hospital, Derby, UK. john.robertson@nottingham.ac.uk
Publication date & source: 2013, Lancet Oncol. , 14(3):228-35
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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