Preliminary efficacy of the anti-insulin-like growth factor type 1 receptor antibody figitumumab in patients with refractory Ewing sarcoma.

Abstract

PURPOSE:

Patients with Ewing sarcoma (ES) with metastases and those who relapse fare poorly and receive therapies that carry significant toxicity. This phase 1/2 study was conducted to evaluate the efficacy of figitumumab in advanced ES.

PATIENTS AND METHODS:

Patients with sarcoma 10 to 18 years old were enrolled in two dose escalation cohorts (20 and 30 mg/Kg intravenously every 4 weeks) in the phase 1 portion of the study. Patients with ES 10 years old or older were enrolled in the phase 2 portion of the study. The primary phase 2 objective was objective response rate (ORR).

RESULTS:

Thirty-one patients with ES (n = 16), osteosarcoma (n = 11), or other sarcomas (n = 4) were enrolled in the phase 1 portion of the study. Dose escalation proceeded to 30 mg/kg every 4 weeks with no dose-limiting toxicity identified. In the phase 2 portion of the study, 107 patients with ES received figitumumab at 30 mg/kg every 4 weeks for a median of 2 cycles (range, 1 to 16). Sixty three percent of phase 2 patients had received at least three prior treatment regimens. Of 106 evaluable patients, 15 had a partial response (ORR, 14.2%) and 25 had stable disease. Median overall survival was 8.9 months. Importantly, patients with a pretreatment circulating free insulin-like growth factor (IGF) -1 lower than 0.65 ng/mL (n = 14) had a median OS of 3.6 months, whereas those with a baseline free IGF-1 ≥ 0.65 ng/mL (n = 84) had a median OS of 10.4 months (P < .001).

CONCLUSION:

Figitumumab had modest activity as single agent in advanced ES. A strong association between pretreatment serum IGF-1 and survival benefit was identified.

• Authors: Heribert Juergens, Najat C Daw, Birgit Geoerger, Stefano Ferrari, Milena Villarroel, Isabelle Aerts, Jeremy Whelan, Uta Dirksen, Mary L Hixon, Donghua Yin, Tao Wang, Stephanie Green, Luisa Paccagnella, Antonio Gualberto
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 29 Issue 34 Pg. 4534-40 (Dec 01 2011) ISSN: 1527-7755 [Electronic] United States
• PMID: 22025154 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Immunoglobulins, Intravenous
• Receptor, IGF Type 1
• figitumumab

Topics

• Adolescent
• Adult
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Bone Neoplasms (drug therapy)
• Female
• Humans
• Immunoglobulins, Intravenous
• Male
• Middle Aged
• Receptor, IGF Type 1 (blood, immunology)
• Recurrence
• Retreatment
• Sarcoma, Ewing (drug therapy)