Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage iii colon cancer: a randomized trial JAMA, 04/05/2012
Alberts SR et al. – Among patients with stage III resected colon cancer, the use of cetuximab with adjuvant mFOLFOX6 compared with mFOLFOX6 alone did not result in improved disease-free survival. Methods
- A randomized trial of 2686 patients aged 18 years or older at multiple institutions across North America enrolled following resection and informed consent between February 10, 2004, and November 25, 2009.
- The primary randomized comparison was 12 biweekly cycles of mFOLFOX6 with and without cetuximab.
- KRAS mutation status was centrally determined.
- The trial was halted after a planned interim analysis of 48% of predicted events (246/515) occurring in 1863 (of 2070 planned) patients with tumors having wild-type KRAS.
- A total of 717 patients with mutated KRAS and 106 with indeterminate KRAS were accrued.
- The 2070 patients with wild-type KRAS provided 90% power to detect a hazard ratio (HR) of 1.33 (2-sided ? = .05), with planned interim efficacy analyses after 25%, 50%, and 75% of expected relapses.
- Median (range) follow-up was 28 (0-68) months.
- The trial demonstrated no benefit when adding cetuximab.
- Three-year disease-free survival for mFOLFOX6 alone was 74.6% vs 71.5% with the addition of cetuximab (HR, 1.21; 95% CI, 0.98-1.49; P = .08) in patients with wild-type KRAS, and 67.1% vs 65.0% (HR, 1.12; 95% CI, 0.86-1.46; P = .38) in patients with mutated KRAS, with no significant benefit in any subgroups assessed.
- Among all patients, grade 3 or higher adverse events (72.5% vs 52.3%; odds ratio [OR], 2.4; 95% CI, 2.1-2.8; P < .001) and failure to complete 12 cycles (33% vs 23%; OR, 1.6; 95% CI, 1.4-1.9; P < .001) were significantly higher with cetuximab. Increased toxicity and greater detrimental differences in all outcomes were observed in patients aged 70 years or older.