Cetuximab (Erbitux®) Combo More Effective Than Cetuximab Alone in Colorectal Cancer
Key Words
Colorectal cancer, cetuximab ( Erbitux®), irinotecan (Camptosar®). (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
A randomized phase II trial showed that the combination of cetuximab (Erbitux®) and irinotecan (CPT-11) shrank tumors in more patients and delayed tumor progression longer than cetuximab alone in patients with metastatic colorectal cancer that had progressed after treatment with standard irinotecan-based chemotherapy.
Source
American Society of Clinical Oncology (ASCO) annual meeting, Chicago, June 1, 2003. (The final results were subsequently published in the July 22, 2004, issue of the New England Journal of Medicine; see the journal abstract.)
Background
Previous phase II trials have also suggested that cetuximab is effective against metastatic colorectal cancer and that the cetuximab/irinotecan combination is more effective than cetuximab alone. This large European study offers independent confirmation of these findings.
Cetuximab is a monoclonal antibody under evaluation that targets the epidermal growth factor receptor (EGFR). Two other new agents that work differently, oxaliplatin and bevacizumab (Avastin®), have also recently shown benefit in trials for advanced and metastatic colorectal cancer. New trials are now being planned or are already under way to compare the new agents in various combinations.
The Study
The randomized phase II trial included 329 patients whose colorectal cancer had progressed after treatment with conventional irinotecan-based chemotherapy. Two-thirds of the patients received cetuximab and irinotecan, and one-third received cetuximab alone. Those who received cetuximab alone had the option to switch to the combination treatment if the single agent failed to stem the disease.
The trial was led by David Cunningham, M.D., of Royal Marsden Hospital, Sutton, England.
Results
The combination therapy shrank tumors in 22.9 percent of patients while the single agent was active in just 10.8 percent. Tumor progression was delayed a median of 4.1 months among those who received the two drugs compared to 1.5 months in the group receiving cetuximab alone. Although the survival time was also longer for the combination regimen – 8.6 months compared to 6.9 months – this difference was not statistically significant - that is, it could have occurred by chance.
One-year survival rates were also about 30 percent for both groups, possibly because patients on cetuximab alone were allowed to cross over to the combination therapy when their tumors stopped responding to the single agent.
The results show that the combination of cetuximab and irinotecan “has significant and important activity in patients resistant to chemotherapy,” said Cunningham.
Limitations
This was a phase II study, designed to show that cetuximab was an active agent in this group of patients. Although the patients were randomized to two groups originally, all received cetuximab and those on the single agent were allowed to switch to the combination therapy before the end of the study. A randomized, controlled, phase III trial is needed to confirm the benefits of cetuximab plus irinotecan.
Also, severe side effects were more frequent among patients receiving the combination therapy. About 65 percent had diarrhea, weakness, low white blood cell counts, rash, or vomiting. About 50 percent of patients receiving cetuximab alone had severe side effects, including difficulty in breathing, weakness, and pain.
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