Reply to A. Grothey et al and R.S. Midgley et al
Authors: Robert J. Mayer
Journal: Journal of Clinical Oncology (2013)

high-risk patients with stage II disease, median postrecurrence survivals were 23.6 months in the fluorouracil with leucovorin arm and 17.3 months in the infusional fluorouracil, leucovorin, and oxaliplatin arm.The last comment by Galle ´n et al 1 referred to the definition of high-risk stage II colon cancer.When the MOSAIC study was designed, there was no consensual definition, especially with regard to a universally valid minimum number of lymph nodes above which there was no risk of understaging. 4Among the 899 patients with stage II disease, 598 (66.5%) had 10 or more nodes examined, and 488 (54.3%) had 12 or more nodes examined.Notably, the median number of lymph nodes was similar in the National Surgical Adjuvant Breast and Bowel Project (NSABP) 07 study. 5ealsothankMidgleyandKerr 6 fortheircommentsonourarticle. 2 We agree with them and with the editorial by Mayer 7 that our trial has not shown a survival benefit from the addition of oxaliplatin to fluorouracil and leucovorin in high-risk patients with stage II colon cancer.However, in these patients with stage II disease, because of the good prognosis, deathsasaresultofothercausesproducedconfusingeffects;therefore,our results might not reflect the individual patient's benefit.We are aware that there were certain statistical limitations to the subgroup analysis of 899 patients with stage II disease in the MOSAIC study. 2 It has been estimated that a prospective clinical trial of adjuvant chemotherapy that includes a nontreatment control arm (which was not the case for patients in the MOSAIC study, in which fluorouracil/leucovorin was the control arm) and is designed to detect a survival benefit of 4% at 5 years in patients with stage II colon cancer with a baseline 5-year survival prognosis of 75% would require at least 4,700 patients. 8Hence, a study for demonstrating an overall survival benefit for patients with stage II disease with oxaliplatin-based chemotherapy is not realistic.Therefore, studies to find prognostic and predictive biomarkers beyond the recognized factors such as T4b to identify the subgroup of patients who could benefit from oxaliplatin and fluorouracil combination chemotherapy are needed.We are also conducting a large translational research project (in collaboration with the NSABP) that is linked to a 10-year follow-up of the MOSAIC study to identify patients who could benefit from oxaliplatin therapy. 9,10 We agree with the observation of Midgley and Kerr 6 that our results do not refer to fluoropyrimidine as a single agent.Hence, we recognize the results observed in the Quasar (Quick and Simple and Reliable) trial (A UKCCR [United Kingdom Coordinating Committee on Cancer Research] Study of Adjuvant Chemotherapy for Colorectal Cancer) and the ACCENT (Adjuvant Colon Cancer Endpoints) meta-analysis that demonstrated the benefit of fluorouracil-based therapy in patients with stage II disease. 11,12 We also share their commitment to mandate an informed discussion and to propose fluoropyrimidine-based treatment in selected patients with stage II disease.We do hope in the near future to acknowledge that adjuvant therapy for stage II colon cancer will be less complicated than it is now.