Results of a phase II cooperative-group trial showed that the targeted agent cetuximab demonstrated minimal activity in patients with advanced, platinum-resistant cervical cancer. No patient had an objective response, and fewer than 15% of patients survived for at least 6 months when treated with the inhibitor of epidermal growth factor receptor (EGFR). A possible suggestion of activity in squamous cell histology tumors offered the only encouragement from an otherwise negative study.
“Although the overall level of activity in the current report does not justify a phase III trial of cetuximab in heavily pretreated, advanced, and recurrent cervical cancer, the current data cannot rule out potential activity of cetuximab in patients harboring cervical tumors with squamous cell histology,” said Alessandro D. Santin, MD, a gynecologic oncologist at Yale University, in a presentation at the recent Society of Gynecologic Oncologists recent meeting in Orlando, Florida.
EGFR is overexpressed in several types of malignancy, including cervical cancer, providing a rationale for evaluating anti-EGFR therapy in the disease. The Gynecologic Oncology Group chose patients with previously treated, metastatic cervical cancer for the clinical evaluation of cetuximab. Eligible patients had recurrent or metastatic cervical cancer with a treatment history of 1 or 2 prior regimens, 1 of which had to be platinum-based. Cetuximab therapy began with a 400-mg loading dose, followed by 250 mg weekly until progression. The primary endpoint was 6-month survival.
Investigators enrolled 35 patients. The trial design required 7 objective responses and for 7 patients to survive progression-free for 6 months or longer as the minimum activity to justify a phase III trial.
Santin reported that no patient had an objective response, and 5 (14.2%) patients survived at least 6 months during treatment with cetuximab. The median progression-free survival (PFS) was 1.97 months, and median overall survival was 6.7 months.
Analysis of response and survival by tumor histology showed that all 5 patients who survived a PFS of at least 6 months had squamous cell histology. In contrast, none of 11 patients with adenosquamous cell or adenocarcinoma histology survived without progression for 6 months.