To evaluate the safety and efficacy of IMC-A12, a human monoclonal antibody (mAb) that blocks insulin-like growth factor receptor-1 (IGF-1R), as monotherapy or in combination with cetuximab in patients with metastatic refractory anti-epidermal growth factor receptor (EGFR) mAb colorectal cancer.
A randomized, phase II study was performed in which patients in arm A received IMC-A12 10 mg/kg intravenously (IV) every 2 weeks, while patients in arm B received this same dose of IMC-A12 plus cetuximab 500 mg/m(2) IV every 2 weeks. Subsequently, arm C (same combination treatment as arm B) was added to include patients who had disease control on a prior anti-EGFR mAb and wild-type KRAS tumors.
Archived pretreatment tumor tissue was obtained when possible for KRAS, PIK3CA, and BRAF genotyping, and immunohistochemistry was obtained for pAKT as well as IGF-1R.
Overall, 64 patients were treated (median age, 61 years; range, 40 to 84 years): 23 patients in arm A, 21 in arm B, and 20 in arm C. No antitumor activity was seen in the 23 patients treated with IMC-A12 monotherapy.
Of the 21 patients randomly assigned to IMC-A12 plus cetuximab, one patient (with KRAS wild type) achieved a partial response, with disease control lasting 6.5 months.
Arm C (all patients with KRAS wild type), however, showed no additional antitumor activity.
Serious adverse events thought possibly related to IMC-A12 included a grade 2 infusion-related reaction (2%; one of 64 patients), thrombocytopenia (2%; one of 64 patients), grade 3 hyperglycemia (2%; one of 64 patients), and grade 1 pyrexia (2%, one of 64 patients).
IMC-A12 alone or in combination with cetuximab was insufficient to warrant additional study in patients with colorectal cancer refractory to EGFR inhibitors.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Department of Medicine, Division of Solid Tumors, Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Howard 1004, New York, NY 10065, USA. reidyd [at] mskcc.org
J Clin Oncol. 2010 Sep;28(27):4240-6
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