CTCs, RAS and BRAF mutations are prognostic factor in mCRC pts. The VISNÚ program was designed to explore the impact of FOLFOXIRI + bevacizumab in a high-risk mCRC group according to CTCs ≥3 (VISNÚ-1) and to compare the efficacy of bevacizumab or cetuximab associated to FOLFIRI in a low-risk group according to CTCs < 3 and RAS wild-type (VISNÚ-2).
Blood samples for CTCs enumeration by Cell Search® method (Menarini – Silicon Biosystems, Inc) were collected at baseline, and samples of tumor tissue were used to determine KRAS-NRAS-BRAF-PIK3CA mutations. This preliminary analysis shows the correlation among CTCs, molecular mutations and clinical characteristics by chi-square analysis.
1208 pts were screened for CTCs and RAS mutation and 590 of them were eligible for the VISNÚ program. In the screening population, CTCs ≥ 3 was found in 40.8%, RAS, BRAF and PI3K mutations were present in 51.4%, 7.5% and 11.3% of pts respectively. No correlation was found among CTCs and RAS, BRAF and PIK3CA mutations (p 0.29, 0.10 and 0.12 respectively). CTCs ≥ 3 was associated with worse ECOG, stage IV, liver, lung and bone metastases, > 2 metastatic sites and CEA levels > 5 ng/ml. RAS mutation correlated with worse ECOG, stage IV, liver, lung and bone metastases, > 2 metastatic sites and CEA levels > 5 ng/ml. BRAF mutation correlated with primary right colon location, and metastases in peritoneum, lymph nodes, bone and liver and high tendency for female (p = 0.058) (Table). PIK3CA mutation was only associated with right primary location and age > 65 years.
CTCs and RAS mutation are significantly associated with other clinical poor prognostic factors. The poor prognosis of BRAF-mutated tumors reported in the literature cannot be explained by its correlation with poor prognostic clinical characteristics.Table:
|Parameters||CTCs> 3 p value||RASmut p value||BRAFmut p value|
|Primary location||–||–||< 0.0001|
|N° organ involved||0.001||0.007||–|
|Stage at diagnosis||0.002||0.02||–|
|CEA levels||< 0.0001||0.02||–|
BRAF mutant less frequently associated to liver involvement
Clinical trial identification
VISNÚ 1: NCT01640405 VISNÚ 2: NCT01640444
Legal entity responsible for the study
Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD)
Roche Farma SA
J.M. Viéitez: Consultant or advisory relationship and research funding: Roche. E. Aranda Aguilar: Honoraria for advisory role from Amgen, Bayer, Celgene, Mecrk, Roche, Sanofi. All other authors have declared no conflicts of interest.