Molecular characterization of metastatic breast cancer F. Bras o-Maristany et al.

No 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 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/m 2 then 250 mg/m 2 weekly) plus FOLFIRI [irinotecan 180 mg/m 2 , leucovorin 400 mg/m 2 , 5-fluorouracil 400 mg/m 2 (bolus) then 2400 mg/m 2 (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 / PIK3C A-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 ...

No abstract