New analysis of colon cancer trial could aid treatment decisions.
The “sidedness” of a primary colon cancer should play a part in treatment decisions for patients whose disease has spread and especially in what targeted agent to use, a researcher said.
In a new analysis of a Phase III trial, patients whose tumors originated on the left side of the colon did better than those with right-sided primary tumors, according to Alan Venook, MD, of the University of California San Francisco.
Importantly, the choice of which targeted agent was added to standard chemotherapy played a “surprising” role in treatment outcomes, Venook told reporters in a briefing in advance of the annual meeting of the American Society of Clinical Oncology (ASCO), starting here June 3.
Venook said the investigators thought before they undertook their analysis that the sidedness of the primary tumor “was not likely to make a big difference.”
But in one arm of the reanalysis, the combination of cetuximab (Erbitux) and chemotherapy resulted in almost a 20-month difference in overall survival.
“This was a dramatic finding,” Venook said.
He said he and colleagues are now conducting molecular studies in the hope of teasing out what underlies the sidedness difference, but in the meantime patients with right- and left-sided tumors “should be treated differently.”
The analysis is based on the large CALGB/SWOG 80405 trial, which looked at outcomes in patients given standard chemotherapy for metastatic colon cancer with the addition of either cetuximab or bevacizumab (Avastin).
Both drugs are approved to treat metastatic colon cancer but they had not previously been compared head to head, commented Richard Schilsky, MD, a former president of ASCO and currently the society’s chief medical officer.
Cetuximab targets the epidermal growth factor receptor (EGFR) while bevacizumab inhibits the vascular endothelial growth factor (VEGF), Schilsky, who is also a study co-author, told MedPage Today earlier.
In the original trial, presented 2 years ago at the ASCO General meeting, neither combination showed a survival advantage over the other, Venook said.
But some small studies have hinted that the sidedness of the primary tumor might affect treatment outcomes, he said. As well, the two sides of the colon arise from different parts of the embryo, so it “would not be surprising” to find that they react differently to treatment.
To investigate the issue, he and colleagues reanalyzed the data by sidedness and treatment combination.
Overall, they found, the median overall survival among the 732 patients with a left-sided tumor was 33.3 months, compared with 19.4 months among those with a right-sided tumor. The difference yielded a hazard ratio for survival of 1.60, with a 95% CI from 1.37 to 1.86, which is significant at P<0.001.
The difference was narrower among patients treated with bevacizumab — 31.4 months among the 356 patients with a left-sided tumor and 24.2 months among those with a right-sided lesion. The 1.297 hazard ratio (95% CI 1.05 to 1.60) was significant at P=0.017.
But it was dramatically better among those treated with cetuximab, Venook said. Those with a left-sided tumor had a median survival of 36 months, compared with 16.7 months for those with a right-sided cancer. The hazard ratio was 1.987 (95% CI 1.60 to 2.46) and was significant at P<0.001.
Venook said sidedness is almost certainly a “surrogate marker” of something more precise and added that he and colleagues are hoping that the molecular analysis will lead to “crisp biological testing.”
But until then, “the sidedness can help us make decisions, in the context of all the other information we gather,” he said.
The report is an illustration of “how very large federally funded studies, such as this one, can really help us to differentiate some of the issues we need to understand to treat our patients,” commented ASCO President Julie Vose, MD, of the University of Nebraska Medical Center in Omaha.
Vose said the study is “definitely going to help us generate hypotheses for future studies.”