The results of a phase III trial testing the efficacy of cetuximab (Erbitux) in combination with cisplatin and capecitabine for patients with advanced gastric adenocarcinoma failed to show a significant improvement in progression-free survival (PFS), when compared to cisplatin and capecitabine alone, announced Merck KGaA, the German pharmaceutical company that distributes cetuximab outside of North America.
The multicenter, open-label, randomized phase III EXPAND trial enrolled 904 patients at 150 centers in 25 countries across Latin America, Europe, Asia Pacific, and Japan. Patients were eligible if they had unresectable advanced gastric cancer or adenocarcinoma of the gastro-esophageal junction (GEJ) and had not received any prior treatment with chemotherapy or radiotherapy. The primary endpoint of the study was PFS.
“We are disappointed that the EXPAND trial did not show a benefit for patients with advanced gastric cancer when Erbitux was added to standard chemotherapy,” said Florian Lordick, MD, Klinikum Braunschweig, Hannover Medical School, Germany, lead investigator of the study, in a statement. “Patients with advanced gastric cancer currently have few treatment choices and a poor prognosis, and we will continue to investigate other treatment options for these patients in the hope of being able to offer improved outcomes.”
The EXPAND trial followed promising results from a phase II trial that was presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in 2008. This trial combined cetuximab with cisplatin and docetaxel in patients with locally advanced or metastatic gastric cancer and showed a disease control rate of 78.6% among 48 patients.
Cetuximab is given as an intravenous infusion and in 2004 it was approved to treat metastatic colon cancer that had been previously treated by chemotherapy. In November 2011, the FDA expanded cetuximab’s approval for squamous cell carcinoma of the head and neck in combination with platinum-based therapy plus 5-florouracil (5-FU) for the first-line treatment of patients with recurrent locoregional disease and/or metastatic disease. However, recent trials have shown that cetuximab failed to improve outcomes in other cancer types. In April, cetuximab did not improve disease-free survival in metastatic colon cancer patients.
Cetuximab, a chimeric monoclonal antibody that specifically targets and inhibits the epidermal growth factor receptor (EGFR), a protein associated with cell proliferation, has been under investigation in a number of different tumor types. Recent positive trials have led the manufacturers of cetuximab to pursue approval of the drug for non-small cell lung cancer, but currently that approval has not been granted.
In North America, Bristol-Meyers Squibb and Eli Lilly and Company distribute cetuximab under its brand name Erbitux.
Pinto C, DiFabio F, Barone C, et al. Cetuximab in combination with cisplatin and docetaxel as first-line treatment in patients with locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (Italian phase II DOCETUX study). J Clin Oncol. 2008;26: 2008 (suppl; abstr 4575).