CETUXIMAB FAILS IN GASTRIC CANCER

July 6, 2012 — A large phase 3 trial in which the targeted therapy cetuximab (Erbitux) was added to standard chemotherapy with cisplatin and capecitabine (Xeloda) to treat gastric cancer has failed to meet its primary end point. The addition of cetuximab did not extend progression-free survival, compared with chemotherapy alone.

This finding was announced in a press release issued by Merck AG, which markets cetuximab in Europe. The actual results of the trial will be presented later this year at a scientific meeting, the company said.

Cetuximab is already approved for use in metastatic colorectal cancer and head and neck cancer.

Results Are Disappointing

This trial, known as EXPAND (Erbitux in Combination With Xeloda and Cisplatin in Advanced Esophagogastric Cancer), involved 904 patients in 24 countries in Asia Pacific, Europe, and Latin America, and in Japan. Patients had unresectable advanced cancer of the stomach or gastroesophageal junction, and had received no previous chemotherapy or radiotherapy in this setting. Usually, these patients would receive palliative chemotherapy only, the company noted.

The results are a disappointment, said lead investigator Florian Lordick, MD, from Klinikum Braunschweig, Hannover Medical School, in Germany.

"Patients with advanced gastric cancer currently have few treatment choices and a poor prognosis. We will continue to investigate other treatment options for these patients in the hope of being able to offer improved outcomes," Dr. Lordick said in a statement.

At the recent World Congress on Gastrointestinal Cancer held in Barcelona, Spain, Dr. Lordick gave a review of the treatment of gastric cancer. He noted that so far, only 1 targeted agent has been approved for use in stomach cancer in combination with chemotherapy — trastuzumab (Herceptin). It was approved for use in HER2-positive gastric tumors after the results of the ToGA trial showed "outstanding overall survival in some patients," he explained. Since then, a number of other targets have been pursued in stomach cancer, and there are a number of trials ongoing, he said.

This trial of cetuximab targeted the epidermal growth-factor receptor, but the results show that this approach was not successful.

Another approach that looked promising in phase 2 trials was the targeting of vascular endothelial growth factor with bevacizumab (Avastin), but Dr. Lordick noted that a phase 3 trial of this approach was also negative.