Eribulin Associated with Less Neuropathy than Ixabepilone

February 2012, Vol 3, No 1 - Breast Cancer

San Antonio, TX—In a randomized phase 2 study of patients with metastatic breast cancer, peripheral neuropathy 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, Weill Cornell Medical College in New York, who presented the study at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium.

“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 end point was the incidence of neuropathy.”

EMBRACE demonstrated that eribulin treatment significantly im­proved median overall survival by 2.5 months compared with standard treatments in patients with heavily pretreated metastatic breast cancer. The overall incidence of peripheral neuropathy in patients who received eribulin was 35% and was mostly mild; grade 3 was seen in 8% of patients and grade 4 in <1%.

The current study prospectively evaluated peripheral neuropathy in 101 patients with heavily pretreated metastatic breast cancer who were randomized to receive either eribulin or ixabepilone as a single agent in 3-week cycles; the mean number of treatment cycles was 6.2 cycles in the eribulin group and 4.8 cycles in the ixabepilone group. Almost one third of patients in each arm had received ≥6 previous agents.

“We found the incidence of neuropathy was about 13% lower with eribulin,” Dr Vahdat reported. Peripheral neuropathy of any grade occurred in 31% of the eribulin group and 44% of the ixabepilone group. Grade 3/4 peripheral neuropathy occurred in 10% versus 20%, respectively. The difference numerically favored eribulin, although 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.”

Figure. Waterfall graphs of percent change in summed longest diameter of target lesions from baseline to nadir in patients receiving a) eribulin or b) ixabepilone according to RECIST (ITT population)
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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 a faster rate of change with eribulin (Figure).

Dr Vahdat acknowledged that if ixabepilone were given weekly, as it often is, the incidence of peripheral neuropathy would be lower. The study followed the US Food and Drug Administration–approved dosing schedule.