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
Javier Sastre, Pilar García‐Alfonso, José María Viéitez, María Teresa Cano, Fernando Rivera, Juan José Reina-Zoilo, Antonieta Salud, Guillermo Quintero, Luis A. Díaz‐Robles, M.J. Safont, A. La Casta, Silvia Gil, Elena Simón Polo, Elena Asensio-Martínez, Beatriz García-Paredes, R.L. López, M. Guillot, Manuel Valladares‐Ayerbes, Enrique Aranda, Eduardo Díaz‐Rubio, José María Viéitez, P. Jiménez, E. Aranda Aguilar, A. Gómez, S. Gil Calle, Antonieta Salud, M. Valladares, B. Graña, Pilar García‐Alfonso, Fernando Rivera, Guillermo Quintero, J.J. Reina, Encarnación González‐Flores, Marcelo Ramos Tejo Salgado, Enrique Grande, C. Guillén, R. Garcia Carbonero, M.J. Flor, M.J. Safont, A. La Casta, Sara Arevalo, Javier Sastre, R. López López, Hermini Manzano, M. Guillot, Xavier Hernandez Yague, A. Arriví, E. Falcó, Javier Gállego, P. Escudero, Ivan Pinos Cabezas, A. Juárez, Elisa Gálvez, Cristina Grávalos, Luis Robles, Elena Simón Polo, Rosario Dueñas, J.M. Campos, A. Albert, P Salínas, Clara Montagut, Mariano Provencio, A. Ruiz Casado, J. Enrique Domínguez‐Muñoz, M. Gil Raga, M.R. Chilet, F.J. González González, Bartomeu Massutí, Anna Mar López, J. Aparicio, M. Marín, J. Alfaro, Montserrat Zanui, David Gutiérrez Abad, A. M. García Tapiador, Carlos García Girón, J. Molina Saera, Esperanza Torres Sánchez, I. López, C. Bosch, A. Arriví, J. Valero, Purificación Martínez de Prado
Abstract
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: (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.