Source: DGNews  |  Posted 1 year ago

By Fred Gebhart

SAN FRANCISCO -- March 19, 2010 -- Clinicians may have a new agent for patients with progressive or recurrent endometrial cancer. New data show that an agent that inhibits epidermal growth factor receptor (EGFR) is clinically active and tolerated by women who have been heavily pretreated with other agents.

“For women with advanced endometrial cancer, treatment options are limited,” said Brian Slomovitz, MD, Women’s Cancer Center, Morristown, New Jersey, on March 16 here at the Society of Gynecologic Oncologists (SGO) 41st Annual Meeting on Women’s Cancer.

“NCCN [National Comprehensive Cancer Network] practice guidelines strongly encourage participation in a clinical trial. There are few other good options. Targeting biological pathways of carcinogenesis is one approach.”

EGFR is overexpressed in the most common histological subtypes of endometrial cancer, according Dr. Slomovitz. EGFR signal transduction is linked with cell proliferation and maturation, cell survival and apoptosis, angiogenesis, and metastasis. Prior research has determined that overexpression of EGFR is associated with both advanced-stage disease and with a poor prognosis.

Prior work has also determined that inhibiting the binding of EGFR and other ligands to the receptor blocks activation of several associated kinases, effectively inhibiting tumour cell growth, activating apoptosis, and decreasing angiogenesis.

Based on the known activity of cetuximab against other cancers, researchers launched an open-label phase 2 trial in endometrial cancer at the University of Texas M. D. Anderson Cancer Center, Houston, Texas and Weill Cornell Medical College, New York, New York.

Researchers enrolled 33 patients with endometrioid (13), serous (12), clear cell (4), and mixed Müllerian (4) tumours. All of the women in the study had measurable recurrent or progressive disease. Among the group, 32 women had received a median of 2 regimens of chemotherapy and 12 had received prior radiotherapy.

The women received an initial cetuximab dose of 400 mg/m² followed by weekly doses of 250 mg/m² for a 4-week cycle. All were treated until progression or toxicity.

The primary endpoint was clinical benefit, either a complete response, partial response, or stable disease for more than 8 weeks by Response Evaluation Criteria in Solid Tumors criteria.

Of the original 33 patients, 23 were evaluable, 1 was removed due to an anaphylactic reaction, and 9 were removed for clinical deterioration. The total clinical response rate was 17% (4 patients), 1 with partial response who remains in the study and 3 with stable disease who eventually progressed.

Rash was the most common adverse event at 72%, Dr. Slomovitz reported, but only 1 patient had a grade 3 rash. Fatigue, nausea, constipation, headache, pain, and vomiting were other common side effects of treatment.

One of the most interesting results, he added, was that rash was found to correlate with response to treatment. When cetuximab is used for colorectal cancer, there is an association between the intensity of rash and clinical outcome, but this study was too small to draw similar conclusions.

“These results suggest that cetuximab can become part of the standard of care for endometrial cancer,” Dr. Slomovitz said. “Translational studies are under way to help identify which patients are most likely to respond to this therapy.”

[Presentation title: Phase II Study of Cetuximab (Erbitux) in Patients With Progressive or Recurrent Endometrial Cancer. Abstract 13]