LOS ANGELES — Cetuximab (Erbitux) prolonged overall survival of patients with metastatic colorectal cancer in one large clinical study and extended progression-free survival for patients in another investigation, according to the results of two large phase III trials presented for the first time at the annual meeting of the American Association for Cancer Research.

In a study conducted by the National Cancer Institute of Canada (NCIC) and the Australasian Gastro-Intestinal Trials Group, 572 patients who had failed two previous rounds of chemotherapy were randomized to receive either best supportive care alone or best supportive care plus cetuximab.

According to Dr. Derek J. Jonker of the University of Ottawa, overall survival increased from a median of 4.6 months to 6.1 months with cetuximab, a monoclonal antibody that inhibits cell growth by binding to the epidermal growth factor receptor. Among patients on cetuximab, 19 (6.6%) had complete or partial responses; none of the patients on best supportive care alone had such improvements. Cetuximab also was associated with a 32% decrease in the risk of progression. These results were statistically significant.

In the Erbitux Plus Irinotecan in Colorectal Cancer (EPIC) trial, 1,298 patients who had failed one previous round of chemotherapy were randomized to receive either irinotecan alone or irinotecan plus cetuximab. According to Dr. Alberto F. Sobrero of Hospital San Marino in Genoa, Italy, the combination resulted in an increase in progression-free survival from 2.6 months to 4.0 months and an increase in the response rate from 4% to 16%, with both differences being statistically significant. There was no statistically significant increase in overall survival, but Dr. Sobrero said this might be because half of the patients in the irinotecan-alone arm crossed over and received cetuximab following the end of the trial.

These studies “give us the preponderance of evidence that we need to conclude that cetuximab is a real drug of use in patients with colorectal cancer,” said Dr. Richard M. Goldberg, of the University of North Carolina at Chapel Hill, at a press briefing. Dr. Goldberg was not directly involved in either trial.

He noted that although these trials present evidence for the use of cetuximab as a second-line or third-line therapy, the drug might also find a use as a first-line therapy. He expects some results from one of the two trials of cetuximab as first-line therapy to be presented at the meeting of the American Society for Clinical Oncology in June. And two additional trials are investigating cetuximab as adjuvant therapy for colorectal cancer.

In the NCIC and EPIC trials, patients received cetuximab at an initial dose of 400 mg/m

Cetuximab is not without side effects. The most common are diarrhea, fatigue, and an acneiform rash, and severe infusion reactions are also possible. The rash, which can be quite troublesome, appears to correlate with treatment effectiveness. Patients who did not experience a skin reaction had a response rate of 4%–5%, while those with severe skin reactions had a 55% response rate, Dr. Sobrero said.

Describing the results of the NCIC trial as “clear and unambiguous,” Dr. Jonker said, “The study is significant because it is the first time that a biologically targeted therapy given on its own has improved survival in colorectal cancer. … There are now five effective types of therapy for the treatment of colorectal cancer. … It's going to be a complex issue to sort out how to best give these drugs in an appropriate sequence.”

In considering the clinical impact of these trials, Dr. Sobrero said, “One thing is running scientific experiments; the other is taking this into the battleground of everyday patient management. That is really tough. … If the patient has indolent disease, he's not heavily symptomatic, why should I bother in going for a combination? I have data showing that if I give [cetuximab] later in the course, I will attain the same survival. So that would be the condition for going for sequential treatment. If I have an aggressive disease, a symptomatic condition, as we very often encounter in our practice, I will be very much tempted to go with the combination.”

Dr. Goldberg noted that “a minority of patients responds to these drugs, but those patients who respond have a very meaningful response in most cases.”

Cetuximab has already received Food and Drug Administration approval for use in colorectal cancer and head and neck cancer. The NCIC trial was supported by ImClone and Bristol-Myers Squibb, which manufacture and distribute the drug. The EPIC trial was supported in part by Bristol-Myers Squibb and Merck.

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Overall survival increased from a median of 4.6 months to 6.1 months with cetuximab. DR. JONKER

Cetuximab Yields Benefits in Colorectal Cancer