Anti-IGF-1 receptor antibody figitumumab active in sarcoma, Ewing’s sarcoma

Figitumumab, a fully human IgG2 monoclonal antibody targeting the insulin-like growth factor-1 receptor, was found to be well tolerated and demonstrated antitumor activity in a phase-1 study of adult and pediatric patients with sarcoma or Ewing’s sarcoma.

Years of prior research had already established that the inhibition of IGF-1 receptor would likely be beneficial in patients with Ewing sarcoma. This study was conducted to test figitumumab’s efficacy against sarcoma and Ewing’s sarcoma.

To do this, researchers enrolled patients into two single-stage expansion cohorts between January 2006 and August 2008. Patients received 20 mg/kg figitumumab. The first cohort comprised patients (n=15) with various sarcoma subtypes aged 18 or older; the second cohort, patients (n=14) with refractory Ewing’s sarcoma aged 9 or older. The most common subtype was Ewing’s sarcoma.

One hundred and seventy-seven cycles of treatment were given throughout the study. The researchers reported that adverse events were “mostly mild-to-moderate in severity.”

Grade-3 adverse events were severe in three patients: one with deep vein thrombosis, one with vomiting and one with back pain. In addition, one other patient had grade-3 increases in aspartate aminotransferase and gammaglutamyltransferase concentrations. Cardiotoxicity was not observed.

Twenty-eight patients were evaluable for response to figitumumab. There were two confirmed responses (one pathological response and one partial response). Both of these were in patients with Ewing’s sarcoma. Furthermore, eight other patients, six with Ewing’s sarcoma, had stabilization of disease lasting a minimum of four months.

“Although not all patients showed figitumumab activity, the relative lack of toxic effects (particularly those that overlap with the traditional cytotoxic agents used in the treatment of sarcomas) suggests that this agent can be readily combined with standard chemotherapy,” wrote Jeffrey A. Toretsky, MD, of the Lombardi Comprehensive Cancer Center, Georgetown University, and Richard Gorlick, MD, of The Albert Einstein College of Medicine, wrote in an accompanying editorial.

However, Toretsky and Gorlick also noted that the tumors of some patients on study progressed “somewhat rapidly” with the use of figitumumab. “Despite the strong preclinical evidence that suggests a universal benefit with inhibiting IGF-1 receptor, the progressive disease seen in some patients indicates that not all tumors are addicted to IGF-1 receptor signaling or develop rapid resistance to the therapy,” they wrote. Therefore, establishing biomarkers that predict response to IGF-1 receptor are necessary in order to identify the subset of patients most likely to respond to this treatment.

Olmos D. Lancet Oncol. 2009;doi:10.1016/S1470-2045(09)70354-7.