Phase II study of figitumumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: clinical activity and molecular response (GORTEC 2008-02).

Abstract

BACKGROUND:

Preclinical studies suggest that insulin-like growth factor-1 receptor (IGF-1R) blockage could be a promising therapeutic target in squamous cell carcinoma of the head and neck (SCCHN). Therefore, we investigated the efficacy and toxicity of figitumumab, an anti-IGF-1R monoclonal antibody, in palliative SCCHN.

PATIENTS AND METHODS:

Patients with palliative SCCHN progressing after platinum-based therapy were treated with figitumumab i.v. 20 mg/kg, every 3 weeks. The primary end point was the disease control rate at 6-8 weeks after treatment initiation. Tumor biopsies and plasma samples were collected before and after figitumumab administration to monitor the molecular response.

RESULTS:

Seventeen patients were included. Only two patients achieved stable disease at 6-8 weeks. Median overall survival and progression-free survival were 63 and 52 days, respectively. The main grade 3-4 adverse event was hyperglycemia (41%). Translational research showed that figitumumab downregulated IGF-1R at the surface of tumor cells with activation of the epidermal growth factor receptor (EGFR) pathway, as shown by the upregulation of p-EGFR in tumor cells (P=0.016), and an increase in the plasma level of tumor growth factor-alpha (P=0.006).

CONCLUSION:

Figitumumab monotherapy has no clinically significant activity in unselected palliative SCCHN.

• Authors: S Schmitz, M-C Kaminsky-Forrett, S Henry, S Zanetta, L Geoffrois, E Bompas, A Moxhon, L Mignion, J Guigay, L Knoops, M Hamoir, J-P Machiels
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 23 Issue 8 Pg. 2153-2161 (Aug 2012) ISSN: 1569-8041 [Electronic] England
• PMID: 22234739 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Antibodies, Monoclonal
• Biopsy
• Carcinoma, Squamous Cell (blood, drug therapy, genetics, pathology)
• Gene Expression Profiling
• Head and Neck Neoplasms (blood, drug therapy, genetics, pathology)
• Humans
• Immunoglobulins, Intravenous (adverse effects, immunology, therapeutic use)
• Receptor, IGF Type 1 (antagonists & inhibitors, immunology)
• Reverse Transcriptase Polymerase Chain Reaction