Eribulin Demonstrates Limited Efficacy in BRAF V600E-Mutated Metastatic Colorectal Cancer

Results from the phase 2 BRAVERY trial show that eribulin, a microtubule inhibitor, demonstrated limited efficacy in previously treated patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC).

“The development of effective novel drugs is vital for improving the prognosis of this patient population,” stated Toshiki Masuishi, MD, Aichi Cancer Center Hospital, Nagoya, Japan, and coauthors. “Based on the reported antitumor effects of microtubule inhibitors in xenograft models of BRAF V600E-mutated mCRC, this multicenter phase 2 study aimed to evaluate the efficacy and safety of eribulin.”

In this open-label, single-arm trial, 27 patients received 1.4 mg/m² of intravenous eribulin on days 1 and 8 of a 3-week cycle until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). Key secondary end points included disease control rate, progression-free survival (PFS), overall survival (OS), and safety. Exploratory biomarker analyses were conducted using tumor and serial blood samples. Patients achieving tumor reduction and/or PFS of >6 months were classified as the good response group, while all others comprised the poor response group.

At analysis, the ORR was 0%. The disease control rate was 41%, median PFS was 1.4 months, and median OS was 5.3 months. The most frequently observed grade 3 or 4 adverse events included neutropenia (63%) and febrile neutropenia (22%). No treatment-related deaths were reported. Among 26 patients with available tumor RNA sequencing data, all 4 patients in the good response group had the BM2 subtype. Among 22 patients in the poor response group, 8 had the BM1 subtype and 14 had the BM2 subtype (P = .07). At the start of the second treatment cycle, the rate of decreasing BRAF V600E relative clonality was 75% in the good response group and 11% in the poor response group (P = .02).

“This phase 2 study demonstrated that eribulin monotherapy as second-line or later treatment achieved a reduction in tumor size but had limited antitumor activity in patients with BRAF V600E–mutated mCRC and did not achieve its primary end point,” concluded Dr Masuishi and colleagues. “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.”

Source:
Masuishi T, Taniguchi H, Kotani D, et al. A multicenter phase 2 study of eribulin for BRAF V600E–mutant metastatic colorectal cancer: The BRAVERY study (EPOC1701). ESMO Open. Published online October 9, 2025. doi:10.1016/j.esmoop.2025.105839