Phase II trial of single agent cetuximab in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with the potential for dose escalation to rash

Abstract

Objectives: Determine if cetuximab dose escalation to induce grade 2 rash correlates with anti-tumor activity and if sera-based markers could predict likelihood of response.

Methods: Patients with persistent/recurrent ovarian or primary peritoneal carcinoma received an initial dose of cetuximab 400 mg/m(2), then 250 mg/m(2) weekly for two 3-week cycles. Patients who had stable disease (SD) and <grade 2 rash were dose escalated in 75 mg/m(2) increments every 3 weeks until grade 2 rash or to a maximum weekly dose of 400 mg/m(2). Pre- and post-treatment serum samples were evaluated for potential predictive markers of response.

Results: One of 25 patients achieved partial remission (PR) and 9 patients had SD. The median progression free survival was 2.1 months; the 1-year survival rate was 54.8%. Rash (96%) was the most common drug-related adverse event. At first response assessment, 4 patients remained at 250 mg/m(2); 8 patients were dose-escalated to 325 mg/m(2); of these, 4 ultimately were increased to 400 mg/m(2). Patients with progressive disease (PD) were removed from the study. Ninety-two serologic markers were analyzed from 20 patients to identify markers associated with clinical activity and/or predictive of outcome. Pretreatment levels of twelve markers were significantly elevated in patients exhibiting PD versus SD or PR; however, changes in marker levels during the course of treatment were not significant indicators of response.

Conclusions: Single-agent cetuximab showed minimal activity in patients with recurrent ovarian cancer. Patients with elevated levels of 12 serologic markers at baseline were more likely to have earlier disease progression.

Fig. 1

Box plots show normalized fluorescent intensity values of protein markers in pretreatment serum samples from patients who displayed SD or a PR (white boxes) and patients who displayed PD (gray boxes). Only markers with a ≥ two-fold difference between the two groups and a ≤10% FDR are shown.

Fig. 2

Box plots show normalized fluorescent intensity values of protein markers in serum samples post treatment from patients who displayed SD or a PR (white boxes) and patients who displayed PD (gray boxes). Only markers with a ≥ two-fold difference between the two groups and a ≤10% FDR are shown.