10-Year Follow-Up of the MOSAIC Trial: Overall Survival and BRAF Mutation Status
The MOSAIC study showed a significant benefit for the addition of oxaliplatin to the fluoropyrimidine 5-fluorouracil (5-FU) and leucovorin (LV) in terms of 3-year disease-free survival (DFS) and in overall survival (OS) in patients with stage II/III resected colon cancer, which led to a universal adoption of the resulting FOLFOX regimen and its modified versions. Andre and colleagues reported the 10-year follow-up of the MOSAIC trial, with updated OS results, as well as survival outcomes analyzed by BRAF mutation status (Andre et al. ESMO 2014: Abstract 502PD).
At a median follow-up of 9.5 years, the 10-year DFS rates in the full population of 2246 patients with stage II/III colon cancer were significantly higher for the FOLFOX4 arms compared with the 5-FULV arms (61.7% vs 67.5% ; HR, 0.82; P = .007). This translated into a significantly higher 10-year OS rate (67.1% vs 71.7%; HR, 0.85; P = .043), with the increase in absolute difference from the 5-year OS rate of 2.1% to 4.6%. In patients with more advanced disease, the improvement in 10-year OS with the FOLFOX4 regimen became more apparent, showing an absolute difference of 8.1% and 13.2% in stage III (HR, 0.80; P = .015) and stage IIIC (HR, 0.70; P = .01) disease, respectively.
Of the 903 samples tested for BRAF mutation, 94 patients were found to harbor BRAF mutations. OS analysis according to BRAF mutation status showed that BRAF mutation was not a prognostic factor; however, FOLFOX4 particularly benefited patients who had the BRAF mutation in the 3-year DFS and 10-year OS. In addition, the dMMR (deficient mismatch repair) biomarker was found to be a prognostic factor as well as a predictor factor in this patient population.
These 10-year follow-up results confirm earlier results of survival benefit with oxaliplatin-based chemotherapy as adjuvant therapy for patients with stage II/III colon cancer.