Linda T. Vahdat, MD
Patients with metastatic breast cancer (MBC) who were treated with eribulin mesylate (Halaven) were less likely to experience peripheral neuropathy (PN) and took longer to develop more severe forms of the disorder than those who received ixabepilone (Ixempra), according to clinical trial data presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium.
The differences in the overall incidence of PN and treatment-emergent neuropathy (TEN) were not statistically significant, but the findings capture part of the picture for the relatively common chemotherapy adverse event, according to Linda T. Vahdat, MD, director of the Breast Cancer Research Program and professor of Medicine at Weill Cornell Medical College, New York, New York.
“There was about a 15% difference, with less peripheral neuropathy in the eribulin group,” said Vahdat, who presented the findings in a poster. “What was really striking was the fact that it took a shorter time to develop peripheral neuropathy with ixabepilone than it did with eribulin.”
The phase II study was aimed at exploring the more favorable PN profile that eribulin demonstrated in prior research, including during the EMBRACE trial that prompted the FDA to approve Halaven in 2010 for previously treated patients with MBC. The agency said Halaven is the first single agent to improve overall survival among late-stage patients, who have few remaining options.
The PN study involved 104 patients with locally recurrent MBC who were randomized to receive either eribulin or ixabepilone during 21-day treatment cycles. All participants had received at least 1 prior chemotherapy regimen containing a taxane, and approximately 32% had been given ≥6 anticancer therapies.
Of 51 patients in the eribulin arm, 16 (31.3%) experienced PN, including 5 (9.8%) with grade ≥3 symptoms. By comparison, 22 of the 50 patients in the ixabepilone group (44%) had PN, including 10 (20%) with grade ≥3 symptoms.
The contrast was more striking in TEN, defined as symptoms that began on day 1 of the first cycle, and/or increased in severity during the study, or started within 30 days of the last dose. The median time to onset of TEN was 35.9 weeks in the eribulin arm versus 11.6 weeks in the ixabepilone group, researchers found.
In addition, investigators reported that fewer patients in the eribulin group discontinued treatment due to PN compared with the ixabepilone group (3.9% vs 18.0%), or overall treatment-emergent adverse events (11.8% vs 32.0%).
PN, which covers symptoms ranging from mild numbness and tingling to loss of muscle function and dizziness, is associated with several types of chemotherapy, including the taxanes paclitaxel and docetaxel, which are frequently given as first-line treatment in MBC.
Vahdat said more work is needed to refine instruments by which oncologists define PN, and that a multidisciplinary approach is necessary to understand the mechanisms of PN and develop strategies to reduce and perhaps prevent the disorder.
Meanwhile, Vahdat said oncology specialists should be vigilant about PN, even when giving eribulin, with its relatively low profile for adverse events.
“It doesn’t really cause significant grade 3/4 neuropathy but it can cause some neuropathy,” she said. “So I think unless you’re looking for it, sometimes you won’t find it, and so that’s why I would say, ask [patients] about peripheral neuropathy, if that’s not what you would normally do.”
Eisai Inc, which developed Halaven, funded the PN study.
Vahdat L, Gopalakrishna P, Garcia AA, et al. Comparison of the incidence of peripheral neuropathy with eribulin mesylate versus ixabepilone in metastatic breast cancer patients: a randomized phase II study. Presented at CTRC-AACR San Antonio Breast Cancer Symposium, San Antonio, TX. December 6-10, 2011. Abstract P5-19-02.