RT Journal Article
T1 Influence of BRAF and PIK3CA mutations on the efficacy of FOLFIRI plus bevacizumab or cetuximab as first-line therapy in patients with RAS wild-type metastatic colorectal carcinoma and <3 baseline circulating tumour cells: the randomised phase II VISNÚ-2 study
A1 Sastre, J.
A1 García-Alfonso, P.
A1 Viéitez, J. M.
A1 Cano, M. T.
A1 Rivera, F.
A1 Reina-Zoilo, J. J.
A1 Salud-Salvia, A.
A1 Quintero, G.
A1 Robles-Díaz, L
A1 Safont, M. J.
A1 La Casta, A.
A1 Gil, S.
A1 Polo, E.
A1 Asensio-Martínez, E.
A1 García-Paredes, B.
A1 López, R. L.
A1 Guillot, M.
A1 Valladares-Ayerbes, M.
A1 Aranda, E.
A1 Díaz-Rubio, E.
K1 BRAF
K1 Colorectal cancer
K1 PIK3CA
K1 RAS
K1 Targeted therapy
K1 Neoplasias colorrectales
K1 Terapia dirigida
K1 Neoplastic cells circulating
K1 Células neoplásicas circulantes
AB Background: We explored the influence of BRAF and PIK3CA mutational status on the efficacy of bevacizumab or cetuximab plus 5-fluorouracil/leucovorin and irinotecan (FOLFIRI) as first-line therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC).Patients and methods: VISNÚ-2 was a multicentre, randomised, phase II study. Patients with RAS wild-type mCRC and <3 circulating tumour cells/7.5 ml blood were stratified by BRAF/PIK3CA status (wild-type versus mutated) and number of affected organs (1 versus >1), and allocated to bevacizumab (5 mg/kg every 2 weeks) or cetuximab (400 mg/m2 then 250 mg/m2 weekly) plus FOLFIRI [irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 (bolus) then 2400 mg/m2 (46-h continuous infusion) every 2 weeks]. The primary endpoint was progression-free survival (PFS). All analyses were exploratory.Results: Two hundred and forty patients with BRAF/PIK3CA wild-type (n = 196) or BRAF- and/or PIK3CA-mutated tumours (n = 44) were enrolled. Median PFS was 12.7 and 8.8 months in patients with BRAF/PIK3CA wild-type and BRAF/PIK3CA-mutated tumours, respectively [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.80-1.85; P = 0.3602]. In the BRAF- and/or PIK3CA-mutated cohort, median PFS was 2.8, 8.8 and 15.0 months in patients with BRAF/PI3KCA-mutated (n = 8), BRAF-mutated/PI3KCA wild-type (n = 16) and BRAF wild-type/PI3KCA-mutated (n = 20) tumours, respectively (P = 0.0002). PFS was similar with bevacizumab plus FOLFIRI versus cetuximab plus FOLFIRI in BRAF/PIK3CA wild-type (HR = 0.99; 95% CI 0.67-1.45; P = 0.9486) and BRAF/PIK3CA-mutated tumours (HR = 1.11; 95% CI 0.53-2.35; P = 0.7820). The most common grade 3/4 treatment-related adverse events were neutropenia, diarrhoea and asthenia in both treatment groups.Conclusions: BRAF/PIK3CA status influences outcomes in patients with RAS wild-type mCRC but does not appear to assist with the selection of first-line targeted therapy.
PB Elsevier Ltd on behalf of European Society for Medical Oncology
YR 2021
FD 2021-03-10
LK http://hdl.handle.net/10668/3917
UL http://hdl.handle.net/10668/3917
LA en
NO Sastre J, García-Alfonso P, Viéitez JM, Cano MT, Rivera F, Reina-Zoilo JJ, et al. Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD). Influence of BRAF and PIK3CA mutations on the efficacy of FOLFIRI plus bevacizumab or cetuximab as first-line therapy in patients with RAS wild-type metastatic colorectal carcinoma and <3 baseline circulating tumour cells: the randomised phase II VISNÚ-2 study. ESMO Open. 2021 Apr;6(2):100062
DS RISalud
RD Apr 7, 2025