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.

Trial registration: ClinicalTrials.gov NCT00560235.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Phase 2 schema. ES, Ewing sarcoma; F, figitumumab.

Fig 2.

Kaplan-Meier curves for (A) progression-free survival and (B) overall survival. 95% CI boundaries are for all phase 2 study patients.

Fig 3.

Association of free and total insulin-like growth factor (IGF) with patient survival. (A) Kaplan-Meier plots for overall survival (OS) of patients with a baseline (cycle 1 day predose) free IGF-1 lower than 0.65 ng/mL (n = 14) versus ≥ 0.65 ng/mL (n = 84). (B) Kaplan-Meier plots for OS of patients with a baseline total IGF-1 lower than 110 ng/mL (n = 17) versus ≥ 110 ng/mL (n = 81). (C) Kaplan-Meier plots for OS by quartile of baseline (cycle 1 day predose) free IGF-1 levels.