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)
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: | https://repository.cshl.edu/id/eprint/33724 |
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