However, after a period of time, a sufficient number of elderly patients died as a result of other causes, diminishing Ponatinib order the OS benefit. The nonsignificant P interaction for age with oxaliplatin treatment suggests that a subset of elderly patients derives a DFS benefit from oxaliplatin. This hypothesis is supported by exploratory analyses in which the data from the three oxaliplatin trials were censored at different time points (Fig 2). If this is truly the explanation, it raises the clinical question of whether increased toxicity from more intensive therapy to delay recurrence is a clinically meaningful benefit, given the competing risks of toxicity and death in older adults. Our study did not include evaluation of biologic agents (bevacizumab and cetuximab) among older patients in the adjuvant setting.

14�C19 However, given the lack of survival benefit noted in the general adjuvant treatment setting, subgroup analyses by age may be less relevant. The ACCENT database provides the advantage of pooling large, mature clinical trials to test hypotheses that are difficult or impossible to test within individual trials. Given the fact that none of the included trials had > one quarter of the patients age �� 70 years, subset analyses by age in the individual studies have limited power. Pooling of the data from these seven trials resulted in > 2,000 patients age �� 70 years to be studied, larger than any subgroup analysis from individual studies. Nonetheless, there are limitations to this analysis. First, the ACCENT analysis lacks toxicity or comorbidity data.

Given the potential benefit of oxaliplatin DFS but not OS, consideration of the toxicity from oxaliplatin should be weighed in decision making regarding the use of oxaliplatin in elderly patients. Second, we do not have data on dose-intensity or proportion of doses delivered compared with the total dose planned. Thus, we were unable to comment on the extent to which the amount of actual dose received may have accounted for this lack of benefit among older patients receiving adjuvant therapy. However, in previously published analyses from the MOSAIC and XELOXA trials, dose-intensity did not alter efficacy of treatment.11,20 Also, only a minority of the elderly receive adjuvant therapy in practice, and an even smaller proportion of highly selected patients enter clinical trials.

Therefore, in an unselected population of patients who may have been ineligible for such trials for many reasons, the degree of benefit may be less than the results reported here. Our study suggests that the competitive risk of dying as a result of other causes may be a mechanism by which older patients do not experience a DFS or OS benefit with combination therapy in the adjuvant setting, in contrast to that GSK-3 noted in the metastatic setting.