R1507, a monoclonal antibody to the insulin-like growth factor 1 receptor, in patients with recurrent or refractory Ewing sarcoma family of tumors: results of a phase II Sarcoma Alliance for Research through Collaboration study

Pappo, A. S., Patel, S. R., Crowley, J., Reinke, D. K., Kuenkele, K. P., Chawla, S. P., Toner, G. C., Maki, R. G., Meyers, P. A., Chugh, R., Ganjoo, K. N., Schuetze, S. M., Juergens, H., Leahy, M. G., Geoerger, B., Benjamin, R. S., Helman, L. J., Baker, L. H. (December 2011) R1507, a monoclonal antibody to the insulin-like growth factor 1 receptor, in patients with recurrent or refractory Ewing sarcoma family of tumors: results of a phase II Sarcoma Alliance for Research through Collaboration study. J Clin Oncol, 29 (34). pp. 4541-7. ISSN 1527-7755 (Electronic)0732-183X (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/22025149
DOI: 10.1200/JCO.2010.34.0000

Abstract

PURPOSE: The type 1 insulin-like growth factor 1 receptor (IGF-1R) has been implicated in the pathogenesis of the Ewing sarcoma family of tumors (ESFT). We conducted a multicenter phase II study of the fully human IGF-1R monoclonal antibody R1507 in patients with recurrent or refractory ESFT. PATIENTS AND METHODS: Patients >/= 2 years of age with refractory or recurrent ESFT received R1507 at doses of 9 mg/kg intravenously one a week or 27 mg/kg intravenously every three weeks. Response was measured by using WHO criteria. Tumor imaging was performed every 6 weeks for 24 weeks and then every 12 weeks. RESULTS: From December 2007 through April 2010, 115 eligible patients from 31 different institutions were enrolled. The median age was 25 years (range, 8 to 78 years). The location of the primary tumor was bone in 57% of patients and extraskeletal in 43% of patients. A total of 109 patients were treated with R1507 9 mg/kg/wk, and six patients were treated with 27 mg/kg/3 wk. The overall complete response/partial response rate was 10% (95% CI, 4.9% to 16.5%). The median duration of response was 29 weeks (range, 12 to 94 weeks), and the median overall survival was 7.6 months (95% CI, 6 to 9.7 months). Ten of 11 responses were observed in patients who presented with primary bone tumors (P = .016). The most common adverse events of grades 3 to 4 were pain (15%), anemia (8%), thrombocytopenia (7%), and asthenia (5%). CONCLUSION: R1507 was a well-tolerated agent that had meaningful and durable benefit in a subgroup of patients with ESFT. The identification of markers that are predictive of a benefit is necessary to fully capitalize on this approach.

Item Type: Paper
Uncontrolled Keywords: Adolescent Adult Aged Antibodies, Monoclonal/*therapeutic use Antineoplastic Agents/*therapeutic use Bone Neoplasms/*drug therapy Child Drug Administration Schedule Humans Middle Aged Receptor, IGF Type 1/*immunology Recurrence Sarcoma, Ewing/*drug therapy Treatment Outcome
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > IGF
diseases & disorders > cancer > drugs and therapies
diseases & disorders > cancer > cancer types > sarcoma
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: 1 December 2011
Date Deposited: 21 Oct 2016 15:42
Last Modified: 21 Oct 2016 15:42
PMCID: PMC3236654
Related URLs:
URI: http://repository.cshl.edu/id/eprint/33724

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