Adding Erbitux® (cetuximab) to standard chemotherapy for stage III colon cancer didn’t improve patient outcomes and added more side effects.
All of the patients in the NO147 trial had cancer that had spread to their lymph nodes and had surgery before beginning chemotherapy. They had normal or wild-type KRAS genes in their tumors.They were randomly assigned to FOLFOX chemotherapy for 6 months or FOLFOX plus Erbitux.
The trial was closed before the planned number of patients were enrolled because an analysis showed that there was no benefit to the additional Erbitux and continuing the trial would not help patients.
NO147 randomized 1,760 patients with wild-type KRAS to either FOLFOX — oxaliplatin, leucovorin, and continuous infusion 5-FU — or FOLFOX plus cetuximab for 12 treatments. The primary goal of the trial was to discover which therapy resulted in the best disease-free survival three years later. Researchers also wanted to measure three-year overall survival and compare serious side effects.
- For all patients there was no difference in disease-free survival with 74.1 percent of patients getting FOLFOX alone disease-free at 3 years compared to 73.3 percent on the FOLFOX plus cetuximab regimen.
- FOLFOX only patients had a trend toward better overall survival with 87.3 percent alive at 3 years compared to 82.1 percent when cetuximab was added.
- Disease-free survival for patients over the age of 70 was worse in the cetuximab arm with 63.8 percent alive without colon cancer at three years compared to 78.0 who only got FOLFOX.
Serious side effects were worse with cetuximab. 65 out of every 100 patients had a grade 3 or worse side effect when they got both FOLFOX and cetuximab compared to 45 of every 100 on the FOLFOX only treatment. In addition to a skin rash that is typical for Erbitux, patients on the drug also had more risk for severe diarrhea.
Fewer patients were able to complete all 12 treatment cycles when cetuximab was added.
Both serious side effects and differences in disease-free and overall survival were increased in patients who were 70 and over.
Erbitux has shown benefits both as a single drug and when it is combined with chemotherapy for patients with metastatic colorectal cancer that has already spread to sites beyond the colon so it was unclear why this benefit didn’t extend to patients without metastases.
Dr. Stephen Alberts, the Mayo Clinic oncologist who led the trial said,
The sum of data to date from trials for metastatic colorectal cancer suggested that cetuximab would provide benefit in these stage III patients with KRAS wild-type tumors, and so our findings are unexpected. It is difficult to understand how an agent that helps patients with metastatic cancer is not beneficial to those with less advanced disease. At this point we are focusing our efforts on identifying a biological explanation for these findings.
He went on,
Based on what we found, any use of cetuximab in stage III colon cancer is not supported by the results of our trial.
Dr. Alberts and the trial team concluded,
In this randomized phase III trial the addition of cetuximab to modifiedFOLFOX6 was of no benefit for patients with resected stage III wild-type KRAS colon cancer.
SOURCE: Alberts et al., 2010 ASCO Annual Meeting Abstracts, #CRA3507
Dr. Alberts discusses the trial and its results below.
Disclosure: C3 has received educational grants from Bristol-Myers Squibb, ImClone, sanofi-aventis, and Pfizer who were sponsors of the NO147 trial in addition to the National Cancer Institute. C3 has ultimate control over content of our website.