In a randomized phase 2 study of metastatic breast cancer patients, peripheral neuropathy (PN) was less likely to occur in patients receiving eribulin mesylate than with ixabepilone.
“Peripheral neuropathy is a big problem in the treatment of breast cancer. Across the spectrum, patients have it, and we don’t know how to treat it,” said Linda T. Vahdat, MD, of Weill Cornell Medical College in New York, who presented the study at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium (Poster P5-19-02).
“If we want to be able to identify patients at risk for peripheral neuropathy and develop strategies to manage it we need to characterize it better. This trial was conceived and started after the close of the EMBRACE trial. It gave us the opportunity to get a better handle on how eribulin performed from the perspective of side effects. The endpoint was the incidence of neuropathy.”
EMBRACE demonstrated that eribulin treatment significantly improved median overall survival by 2.5 months compared with standard treatments in heavily pretreated metastatic breast cancer patients. The overall incidence of PN in eribulin-treated patients was 35% and was mostly mild; grade 3 was seen in 8% and grade 4 in <1%.
The current study prospectively evaluated PN in 101 heavily pretreated metastatic breast cancer patients who were randomized to eribulin or ixabepilone as single agents on an every-3-week schedule; the mean number of treatment cycles was 6.2 in the eribulin group and 4.8 in the ixabepilone group. Almost one-third of patients in each arm had received at least 6 prior agents.
“We found the incidence of neuropathy was about 13% lower with eribulin,” Vahdat reported. PN of any grade occurred in 31% of the eribulin group and 44% of the ixabepilone group. Grade 3/4 PN occurred in 10% versus 20%, respectively. The difference numerically favored eribulin, though it was not statistically significant, she added.
“Most importantly,” she said, “the median time to the onset of treatment-emergent neuropathy was longer in the eribulin group: 36 weeks versus only about 12 weeks with ixabepilone. By cycle 4, only 24% of patients receiving eribulin had developed neuropathy, compared to 44% receiving ixabepilone.”
In addition, safety end points, including objective response rate and progression-free survival, based on Response Evaluation Criteria in Solid Tumors, showed greater reduction in the longest diameter of target lesions (ie, reducing tumor size) with eribulin (~80%) compared with ixabepilone (~70%) from baseline to nadir, as well as faster rate of change with eribulin, as shown in the Figure.
Vahdat acknowledged that if ixabepilone were given weekly, as it often is, the incidence of PN would be lower. The study followed the FDA-approved dosing schedule.