Is Oxaliplatin Useful in Early- Stage Colon Cancer?
Is Oxaliplatin Useful in Early- Stage Colon Cancer?
Hello. I am David Kerr, Professor of Cancer Medicine at University of Oxford and past President of ESMO (European Society for Medical Oncology). Today I would like to discuss some updated results from the MOSAIC trial about the benefits, or otherwise, of oxaliplatin in the adjuvant treatment of early-stage colon cancer.
This is an update of the trial by my friends Christophe Tournigand and Aimery De Gramont. You may remember that they randomly assigned about 2200 patients to infusion of fluorouracil/leucovorin vs infusion of fluorouracil/leucovorin plus oxaliplatin, the so-called FOLFOX4 regime. Of these patients, 899 had stage II disease. Of those 899 patients, 330 were categorized as low-risk and the remainder as high-risk. A high-risk stage II colon cancer patient was somebody with T4 disease, someone who had perforated or obstructed tumor, someone with good evidence of venous invasion or who had less than 10 nodes examined by the pathologist, and patients with tumors that were considered poorly differentiated. What they found with analysis that is now pretty mature -- median follow-up and overall survival is now almost 7 years -- was that oxaliplatin adds no benefit at all for stage II disease. Let me say that once again: Oxaliplatin adds no benefit at all for stage II disease. They also looked at a subgroup of the elderly, about 350 patients out of the entire trial. The elderly were defined as patients between the ages of 70 and 75 years. In this subgroup retrospective analysis, they found that there were no benefits from adding oxaliplatin to infusion of fluorouracil/leucovorin.
There are 2 important things to pick up on here. One is that the treatment of stage II disease is fairly linked to treatment with fluoropyrimidines. Our QUASAR study is the largest, most informative trial and the only one to show a definite survival benefit of 3%-4%. I think that if one starts to use prognostic tools like the OncoType DX Colon Cancer Assay, in which there is a molecular signature that can define which stage II patients are at highest risk for recurrence, using a fluoropyrimidine in that setting might be the logical way to try to select patients who would benefit most from chemotherapy. In terms of the elderly, when we analyzed the QUASAR trial and did a forest plot, I must admit that we saw the benefits falling off quite sharply for patients aged 70 years and older. It is interesting that when we look at trials, whether they are reported in the Journal of Clinical Oncology, Annals of Oncology,Lancet, or New England Journal of Medicine, the median age of patients recruited is always 60, whereas the average age of patients in the clinic is always around 72 or 73. I think it causes us to challenge our therapeutic approach to the elderly.
Therefore, fluoropyrimidines are what we would recommend, and possibly capecitabine or good old plain fluorouracil/leucovorin. For stage II patients, perhaps we can define a worse risk for relapse. I would say that a more modern discriminator of that would be something like the gene signature OncoType DX. Also, we should really challenge ourselves when we sit down with an elderly patient, because treating the elderly with oxaliplatin is no longer approved.
As always, thanks for listening.
Hello. I am David Kerr, Professor of Cancer Medicine at University of Oxford and past President of ESMO (European Society for Medical Oncology). Today I would like to discuss some updated results from the MOSAIC trial about the benefits, or otherwise, of oxaliplatin in the adjuvant treatment of early-stage colon cancer.
This is an update of the trial by my friends Christophe Tournigand and Aimery De Gramont. You may remember that they randomly assigned about 2200 patients to infusion of fluorouracil/leucovorin vs infusion of fluorouracil/leucovorin plus oxaliplatin, the so-called FOLFOX4 regime. Of these patients, 899 had stage II disease. Of those 899 patients, 330 were categorized as low-risk and the remainder as high-risk. A high-risk stage II colon cancer patient was somebody with T4 disease, someone who had perforated or obstructed tumor, someone with good evidence of venous invasion or who had less than 10 nodes examined by the pathologist, and patients with tumors that were considered poorly differentiated. What they found with analysis that is now pretty mature -- median follow-up and overall survival is now almost 7 years -- was that oxaliplatin adds no benefit at all for stage II disease. Let me say that once again: Oxaliplatin adds no benefit at all for stage II disease. They also looked at a subgroup of the elderly, about 350 patients out of the entire trial. The elderly were defined as patients between the ages of 70 and 75 years. In this subgroup retrospective analysis, they found that there were no benefits from adding oxaliplatin to infusion of fluorouracil/leucovorin.
There are 2 important things to pick up on here. One is that the treatment of stage II disease is fairly linked to treatment with fluoropyrimidines. Our QUASAR study is the largest, most informative trial and the only one to show a definite survival benefit of 3%-4%. I think that if one starts to use prognostic tools like the OncoType DX Colon Cancer Assay, in which there is a molecular signature that can define which stage II patients are at highest risk for recurrence, using a fluoropyrimidine in that setting might be the logical way to try to select patients who would benefit most from chemotherapy. In terms of the elderly, when we analyzed the QUASAR trial and did a forest plot, I must admit that we saw the benefits falling off quite sharply for patients aged 70 years and older. It is interesting that when we look at trials, whether they are reported in the Journal of Clinical Oncology, Annals of Oncology,Lancet, or New England Journal of Medicine, the median age of patients recruited is always 60, whereas the average age of patients in the clinic is always around 72 or 73. I think it causes us to challenge our therapeutic approach to the elderly.
Therefore, fluoropyrimidines are what we would recommend, and possibly capecitabine or good old plain fluorouracil/leucovorin. For stage II patients, perhaps we can define a worse risk for relapse. I would say that a more modern discriminator of that would be something like the gene signature OncoType DX. Also, we should really challenge ourselves when we sit down with an elderly patient, because treating the elderly with oxaliplatin is no longer approved.
As always, thanks for listening.
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