Phase II Trial of Cetuximab in Patients With Metastatic or Locally Advanced Soft Tissue or Bone Sarcoma

Background: The epidermal growth factor receptor (EGFR) tyrosine kinase is overexpressed in many sarcoma subtypes. In vitro studies suggest a role of the EGFR pathway in growth and differentiation in some sarcomas. We conducted a phase II trial of cetuximab, a monoclonal antibody to EGFR, in patients with advanced sarcomas. Methods: Cetuximab was administered intravenously as a loading dose on 400 mg/m(2) on day 1, cycle 1 and subsequently 250 mg/m(2) on days 1, 8, 15, and 21 of a 28 day cycle. Using a Simon 2-stage design, 21 EGFR(+) patients were to be accrued in the first stage, with an additional 11 patients if >3 patients met the primary endpoint of 4-month progression-free survival (PFS). An exploratory subgroup of EGFR(-) patients was also included. Results: Twenty-one and 15 evaluable patients enrolled in the EGFR(+) and EGFR(-) subgroup, respectively. One of 21 EGFR(+) patients (4.8%) achieved 4-month PFS. Median PFS and overall survival were 1.7 months [95% confidence interval (CI), 1.6-1.8] and 7.7 months (95% CI, 4.2-10.7), respectively. Three of 15 EGFR(-) patients (20%) achieved 4-month PFS. Median PFS and overall survival were 1.8 months (95% CI, 0.8-2.5) and 15.7 months (95% CI, 7.7-25.3), respectively. No responses were seen in either group. There was no correlation between clinical outcomes and expression of MAP-K, PTEN, and phospho-EGFR. Conclusions: Cetuximab is not an active as a single agent in advanced sarcoma. Further study of anti-EGFR therapy in sarcoma should only be considered after identification of molecular abnormalities predictive of benefit.