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 on day 1, cycle 1 and subsequently 250 mg/m 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.