6533b7defe1ef96bd12765dc

RESEARCH PRODUCT

Mosaic Study: Actualization of Overall Survival (Os) with 10 Years Follow Up and Evaluation of Braf. By Gercor and Mosaic Investigators

subject

description

ABSTRACT Aim: The MOSAIC study (Andre T, N Engl J Med, 2004) has demonstrated in patients with stage II/III resected colon cancer (CC) a benefit of oxaliplatin added to 5FU and LV (LV5FU) in 3-year disease-free survival (DFS) and in overal survival (OS). LV5FU and oxaliplatin (FOLFOX4) has also shown a benefit in deficient MisMatch Repair (dMMR) CC pts (Flejou JF, J Clin Oncol 31: 2013;suppl; abstr 3524). We report here 1) Results of MOSAIC after 10 year follow-up, and 2) results in the BRAF evaluable population. Methods: Of the 2246 patients included in the MOSAIC study (whole population), the actualization of survival data was done with 10 yrs follow up. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks or slides were available in 903 patients for the research of the BRAF V600E mutation (BRAF population) using a preamplification method followed by Amplification Refractory Mutation System (ARMSO) technology. Positive mutants were confirmed by pyrosequencing. Fifteen variables were evaluated in univariate and multivariate analysis as prognostic factors for DFS in the BRAF population. Results: 1) 10yr-DFS rates were 61.7% and 67.5% (HRDFS 0.82; P = 0.007) and 10yr-OS rates were 67.1% and 71.7% (HROS 0.85, P = 0.043) in LV5FU and FOLFOX4 arms, respectively (median follow-up of 9.5 yrs). In stage III pts, HR for DFS and OS were 0.79 (p = 0.007) and 0.80 (P = 0.015), respectively. 2) A total of 94 (10.4%) pts were BRAF mutated. Survivals according to BRAF mutational status are presented in Table 1. In multivariate analysis (n = 903), mutated BRAF was not prognostic for DFS (p = 0.82) while dMMR was prognostic in both univariate and multivariate analyses. Table 1. 3yr-DFS and 10yr-OS rates according to BRAF mutational status. Stage II and III 3-year DFS, % (SE) 10-yr OS, % (SE) BRAF mutated (n = 94)–FOLFOX4 (n = 50)–LV5FU2 (n = 44) HR (95% CI) P-value 80.0 (5.7) 63.6 (7.2) 0.50 (0.25-0.99) 0.046 75.8 (6.1) 65.7 (7.2) 0.66 (0.31-1.41) 0.287 BRAF wild type (n = 809)–FOLFOX4 (n = 413)–LV5FU2 (n = 396) HR (95% CI) P-value 78.4 (2.0) 76.1 (2.1) 0.90 (0.72-1.12) 0.338 70.3 (2.3) 68.4 (2.4) 0.94 (0.73-1.20) 0.599 Conclusions: At 10 years follow up, benefit of oxaliplatin as adjuvant therapy for stage II/III CC is confirmed for DFS and OS. Patients with tumor with BRAF mutation seem to benefit from FOLFOX4. Disclosure: T. Andre: TA received consultancy fees for Advisory board and honoraria from Sanofi. A. De Gramont: AdG received consultancy fees for Advisory board and honoraria from Sanofi.All other authors have declared no conflicts of interest.