ASCO Abstract # 3518
Patients with stage II colon cancer who have a specific defect in the ability to repair their DNA do not benefit from a common type of chemotherapy, says a research team from Mayo Clinic. They do fine with just surgery.
The scientists say their findings, to be presented at the June 4-8 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, suggest that stage II patients should have a simple, affordable test to check the status of their mismatch repair (MMR) proteins. Those patients with deficient MMR (dMMR) do not benefit from treatment with a common regimen of rapid infusion 5FU and leucovorin.
The study is likely the most definitive to date on the connection between dMMR and treatment and outcome of stage II colon cancer, says the lead author, George P. Kim, M.D., an oncologist at the Mayo Clinic campus in Florida.
“We find that adding this particular chemotherapy to surgery in stage II colon cancer patients who have dMMR does not add any benefit at all, and may just contribute some toxicity,” says Dr. Kim. “In short, there is no reason to give this common chemotherapy to these patients.”
Dr. Kim adds that approximately 20 percent of stage II colon cancer patients have dMMR, but that up to 40 percent of all stage II patients are receiving chemotherapy. Some of those patients may be receiving other chemotherapy regimens, and it is not clear that dMMR status negates the benefits of those regimens as well, he says.
“We would think it wouldn’t make a difference but we haven’t studied the effect in other treatments. I think it is fair to say that some patients are receiving chemotherapy when they don’t benefit from it,” Dr. Kim says.
This latest analysis combined data from several phase III clinical trials, involving 1,562 patients, and included specimens from the (NSABP). The researchers from the Mayo Clinic campus in Florida combined their dataset with that of several other trials conducted in the United States and Europe and previously presented by Daniel Sargent, Ph.D. from the Mayo Clinic campus in Minnesota. Previously, Dr. Sargent’s team had initially looked at MMR status in relation to treatment outcomes, but the researchers now were able to include additional patients.
In the new findings presented at ASCO, Dr. Kim and team found a dMMR effect in stage II patients but not in lymph node-positive or stage III patients. “Stage III colon cancer patients need to continue to be treated with chemotherapy, despite their MMR status,” Dr. Kim says.
Treatment in stage II cancer was a different story. “From the beginning, patients with dMMR had a good prognosis, low risk of recurrence, and excellent disease-free and overall-survival,” he says. “The benefit of dMMR status never waivered. It was constant over time.”
Researchers have hypotheses as to why patients with dMMR do not benefit from chemotherapy, but no definitive answers at the present time. “In laboratory studies we have seen that loss of DNA repair enzymes makes cancer resistant to chemotherapy, but it isn’t clear why this translates to benefit,” Dr. Kim says. “Given that lack of a clear biological basis, I can understand why oncologists may be reluctant to use a MMR test, but these findings should assure them.”
Below is a link to an edited youtube video with Dr. Kim.