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Updated: May 25, 2026
A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing (Neo)adjuvant Therapies
Published on: July 28, 2020
Phase II trial of cetuximab in patients with metastatic or locally advanced soft tissue or bone sarcoma
Huan T Ha1, Kent A Griffith, Mark M Zalupski
1Moses Cone Reg Cancer Ctr., Greensboro, NC, USA.
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.
Insights
Cetuximab showed limited efficacy as a single agent for advanced sarcoma patients, with low progression-free survival rates. Future anti-EGFR therapy requires identifying predictive molecular markers for better patient selection.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase is overexpressed in various sarcoma subtypes.
- In vitro studies indicate a potential role for the EGFR pathway in sarcoma growth and differentiation.
Purpose of the Study:
- To evaluate the efficacy of cetuximab, an EGFR-targeting monoclonal antibody, in patients with advanced sarcomas.
- To assess the primary endpoint of 4-month progression-free survival (PFS) in a phase II clinical trial.
Main Methods:
- A phase II clinical trial using a Simon 2-stage design.
- Patients received cetuximab intravenously: a 400 mg/m loading dose, followed by 250 mg/m every week.
- Accrued 21 patients in stage 1, with potential for 11 more based on PFS.
Main Results:
- Only 4.8% of 21 patients in the main cohort achieved 4-month PFS; median PFS was 1.7 months.
- In an exploratory subgroup of 15 patients, 20% achieved 4-month PFS; median PFS was 1.8 months.
- No objective responses were observed, and outcomes did not correlate with MAP-K, PTEN, or phospho-EGFR expression.
Conclusions:
- Cetuximab demonstrated limited activity as a single agent in advanced sarcoma.
- Further investigation into anti-EGFR therapy for sarcoma necessitates the identification of predictive molecular abnormalities.
