Details

Autor(en) / Beteiligte

• Sastre, J.
• García-Alfonso, P.
• Viéitez, J.M.
• Cano, M.T.
• Rivera, F.
• Reina-Zoilo, J.J.
• Salud-Salvia, A.
• Quintero, G.
• Robles-Díaz, L.
• Safont, M.J.
• La Casta, A.
• Gil, S.
• Polo, E.
• Asensio-Martínez, E.
• García-Paredes, B.
• López, R.L.
• Guillot, M.
• Valladares-Ayerbes, M.
• Aranda, E.
• Díaz-Rubio, E.
• Jiménez, P.
• Aguilar, E. Aranda
• Gómez, A.
• Gil Calle, S.
• Salud, A.
• Valladares, M.
• Graña, B.
• Reina, J.J.
• González Flores, E.
• Salgado, M.
• Grande, E.
• Guillén, C.
• Garcia Carbonero, R.
• Flor, M.J.
• Arévalo, S.
• López López, R.
• Manzano, H.
• Hernández Yagüe, X.
• Arrivi, A.
• Falcó, E.
• Gallego, J.
• Escudero, P.
• Cabezas, I.
• Juárez, A.
• Gálvez, E.
• Grávalos, C.
• Robles, L.
• Dueñas, R.
• Campos, J.M.
• Albert, A.
• Salinas, P.
• Montagut, C.
• Provencio, M.
• Ruiz Casado, A.
• Muñoz, J.
• Gil Raga, M.
• Chilet, M.R.
• González González, F.J.
• Massutí, B.
• López, A.
• Aparicio, J.
• Marín, M.
• Alfaro, J.
• Zanui, M.
• Gutiérrez Abad, D.
• García Tapiador, A.M.
• García-Girón, C.
• Molina Saera, J.
• Torres Sánchez, E.
• López, I.
• Bosch, C.
• Valero, J.
• Martínez de Prado, P.

Titel

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

Ist Teil von

• ESMO open, 2021-04, Vol.6 (2), p.100062-100062, Article 100062

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2021

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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). 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. 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. 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. •This study examined if BRAF/PIK3CA mutational status can guide therapy in RAS wild-type mCRC.•BRAF mutations were associated with poorer survival outcomes, and were potentiated by PI3KCA mutations.•Bevacizumab-FOLFIRI versus cetuximab-FOLFIRI had similar outcomes in BRAF /PIK3CA wild-type and BRAF /PIK3CA-mutated tumours.•BRAF and PI3KCA mutations have a role as prognostic but not predictive factors.