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

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J.M. Viéitez¹  M.T. Cano²  F. Rivera³  J.J. Reina-Zoilo⁴  A. Salud-Salvia⁵  G. Quintero⁶  L. Robles-Díaz⁷  M.J. Safont⁸  A. La Casta⁹  S. Gil^1,10  E. Polo^1,11  E. Asensio-Martínez^1,12  B. García-Paredes^1,13  R.L. López^1,14  M. Guillot^1,15  M. Valladares-Ayerbes^1,16  E. Aranda²  E. Díaz-Rubio^1,13  J. Sastre^1,13  P. García-Alfonso^1,17 

[1] Medical Oncology, Hospital Universitario Central de Asturias;Medical Oncology, IMIBIC, Reina Sofía Hospital, University of Córdoba, CIBERONC, Instituto de Salud Carlos III;Medical Oncology, Hospital Universitario Marqués de Valdecilla;Medical Oncology, Complejo Hospitalario Virgen de la Macarena;Hospital Universitario Arnau de Vilanova de Lleida;Medical Oncology, Hospital Lucus Augusti;Medical Oncology, Hospital 12 de Octubre;Medical Oncology, Hospital General Universitario de Valencia;Medical Oncology, Hospital de Donostia;Medical Oncology, Hospital Universitario Regional y Virgen de la Victoria;Medical Oncology, Hospital Miguel Servet;Medical Oncology, Hospital General Universitario de Elche;Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación Hospital Clínico San Carlos;Medical Oncology, University Clinical Hospital and Health Research Institute ,(IDIS), CIBERONC, Santiago de Compostela University School of Medicine;Medical Oncology, Hospital Son Espases;Medical Oncology, Complejo Hospitalario Universitario A Coruña, Instituto de Investigación Biomédica;Medical Oncology, Hospital Universitario Gregorio Marañón

关键词: BRAF;    colorectal cancer;    PIK3CA;    RAS;    targeted therapy;   

DOI  :  10.1016/j.esmoop.2021.100062

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

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/PIK3CA1), 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.

【 授权许可】

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