A multicenter phase II study of eribulin for BRAF V600E mutant metastatic colorectal cancer: the BRAVERY study (EPOC1701).

BACKGROUND: Based on the reported antitumor effects of microtubule inhibitors in xenograft models of BRAF V600E mutant colorectal cancer, this multicenter phase II study aimed to evaluate the efficacy and safety of eribulin in patients with BRAF V600E mutant metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with BRAF V600E mutant mCRC who received at least one prior regimen were administered intravenous eribulin. The primary endpoint was the objective response rate (ORR). Biomarker analyses were carried out using tumor and serial blood samples. Patients with reduced tumor size and/or progression-free survival (PFS) of >6 months were classified into the good response group, and the remaining patients were classified into the poor response group. RESULTS: Among the 27 patients enrolled, the ORR was 0% (95% confidence interval 0.0% to 12.8%), the disease control rate was 41%, the median PFS was 1.4 months, and the median survival time was 5.3 months (median follow-up, 5.3 months). Of 26 patients for whom tumors for RNA sequencing were available, all four patients in the good response group had the BRAF mutant (BM)2 subtype on gene expression analysis of BM subtype, whereas 22 patients in the poor response group had the BM1 (n = 8) or BM2 (n = 14) subtypes (P = 0.07). The proportion of patients with decreasing BRAF V600E relative clonality at the start of the second cycle was 75% and 11% in the good response and poor response groups, respectively (P = 0.02). Grade 3 and 4 adverse events included neutropenia (63%) and febrile neutropenia (22%). CONCLUSIONS: This phase II study of eribulin for patients with BRAF V600E mutant mCRC did not meet the primary endpoint. Although BM2 on gene expression analysis of BM subtype may be a predictive marker of eribulin efficacy, further studies are required to validate this hypothesis.