Clinical and Translational Results of a Phase II, Randomized Trial of an Anti-IGF-1R (Cixutumumab) in Women with Breast Cancer That Progressed on Endocrine Therapy.
Clin Cancer Res
; 22(2): 301-9, 2016 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-26324738
ABSTRACT
PURPOSE:
This phase II trial evaluated the efficacy and safety of cixutumumab, a human anti-insulin-like growth factor receptor 1 (IGF-1R) monoclonal IgG1 antibody, and explored potential biomarkers in postmenopausal women with hormone receptor-positive breast cancer. EXPERIMENTALDESIGN:
Patients with hormone receptor-positive breast cancer that progressed on antiestrogen therapy received (21 randomization) cixutumumab 10 mg/kg and the same antiestrogen (arm A) or cixutumumab alone (arm B) every 2 weeks (q2w). Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and safety. Correlative analyses of IGF-1R, total insulin receptor (IR), and IR isoforms A (IR-A) and B (IR-B) expression in tumor tissue were explored.RESULTS:
Ninety-three patients were randomized (arm A, n = 62; arm B, n = 31). Median PFS was 2.0 and 3.1 months for arm A and arm B, respectively. Secondary efficacy measures were similar between the arms. Overall, cixutumumab was well tolerated. IGF-1R expression was not associated with clinical outcomes. Regardless of the treatment, lower IR-A, IR-B, and total IR mRNA expression in tumor tissue was significantly associated with longer PFS [IR-A HR, 2.62 (P = 0.0062); IR-B HR, 2.21 (P = 0.0202); and total IR HR, 2.18 (P = 0.0230)] and OS [IR-A HR, 2.94 (P = 0.0156); IR-B HR, 2.69 (P = 0.0245); and total IR HR, 2.72 (P = 0.0231)].CONCLUSIONS:
Cixutumumab (10 mg/kg) with or without antiestrogen q2w had an acceptable safety profile, but no significant clinical efficacy. Patients with low total IR, IR-A, and IR-B mRNA expression levels had significantly longer PFS and OS, independent of the treatment. The prognostic or predictive value of IR as a biomarker for IGF-1R-targeted therapies requires further validation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
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Receptor IGF Tipo 1
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Moduladores de los Receptores de Estrógeno
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Anticuerpos Monoclonales
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2016
Tipo del documento:
Article