Benefit of FOLFOX4 Confirmed at 4-Year Follow-up of MOSAIC Trial

PARIS, FRANCE-Analysis of disease-free survival data at 4 years into the MOSAIC trial "amplifies the benefit of FOLFOX4 obtained at 3 years," reported the trial's lead investigator, Aimery de Gramont, MD, of Hôpital Saint Antoine in Paris (abstract 3501). The MOSAIC (Multicenter International Study of Oxaliplatin(Drug information on oxaliplatin)/FU-LV in the Adjuvant Treatment of Colon Cancer) trial was designed to demonstrate an increase in disease-free sur- vival in stage II and III colon cancer. At a median follow-up of 56.2 months, the disease-free survival rate was 69.8% in patients receiving fluorouracil(Drug information on fluorouracil)/leucovorin (5-FU/LV) and 76.4% in patients receiving FOLFOX4 (fluorouracil, leucovorin, oxaliplatin [Eloxatin]). This 6.6% difference (P > .001; hazard ratio [HR] = .77) in diseasefree survival between the two arms of the study translates into a 23% reduction in the risk of relapse, Dr. de Gramont said. Clearer Benefit in Stage III Disease For patients with stage II disease (40% of both arms), the difference in disease-free survival was 3.5%, and for patients with stage III disease (60%), the difference was 8.6%, favoring the FOLFOX4 arm. "The majority of the benefit is clearer in stage III, but we see a difference in stage II. I don't think this is either an endorsement or indictment for using this regimen in stage II," noted Leonard B. Saltz, MD, of Memorial Sloan-Kettering Cancer Center in New York, a discussant for this ASCO presentation. "Patients who are higher risk stage II clearly have a prognosis appropriate to be considered along with the best therapies for stage III. For the lower risk stage II patients, I think toxicity issues have to be considered," Dr. Saltz added. In patients with stage III disease and fewer than four positive nodes, the difference in survival was 7.2%; in patients with more than four positive nodes, "the difference was an impressive 11.5%," Dr. de Gramont said. "This study has met elegantly its primary objective and this is why FOLFOX has been registered to treat patients with stage III colon cancer," he concluded. Data were reported for 1,123 patients in each of the study arms. Overall survival at 4 years was 82.8% in the 5-FU/LV arm and 84.9% in the FOLFOX4 arm. Notably, there were fewer patients alive with recurrence in the FOLFOX4 arm than in the 5-FU/LV arm (83 patients [7.4%] vs 134 patients [11.9%]). "With the difference in patients alive with recurrence, there is no doubt that the final difference in survival will be significant," Dr. de Gramont said. The relapse rate was 24.8% in the FOLFOX4 study arm and 30.7% in the 5-FU/LV arm. Long-term Safety Grade 3/4 neutropenia was much more common among patients receiving oxaliplatin, occurring in 41% of those in the FOLFOX4 arm and 4.7% of those in the 5-FU/LV arm (see Table 1). Febrile neutropenia was uncommon in both arms, affecting 1.8% of the FOLFOX4 arm and 0.2% of the 5-FU/LV arm. "GI toxicity was mild, and that is a good reason to keep the FOLFOX4 regimen in the next adjuvant studies," Dr. de Gramont said. Neuropathy occurred among 12.4% of patients in the FOLFOX4 arm but was completely resolved in 80% of patients and at least partially resolved in almost all patients. Long-term safety was demonstrated by no significant increase in second cancers.