P5-19-02: Comparison of the Incidence of Peripheral Neuropathy with Eribulin Mesylate Versus Ixabepilone in Metastatic Breast Cancer Patients: A Randomized Phase II Study.
Authors: Vahdat L , Gopalakrishna P , Garcia AA , Vogel C , Pellegrino C , Lindquist D , Iannotti N 
Published: June 2012

Abstract
Background
Peripheral neuropathy (PN) is a common toxicity and treatment limiting factor in heavily pretreated patients (pts) with metastatic breast cancer (MBC). Consequently, tolerability is important when choosing treatment. Eribulin mesylate has recently been approved in the US for patients with MBC who have previously received at least two chemotherapeutic regimens for metastatic disease including an anthracycline and a taxane. Eribulin was associated with a 34.6% incidence of PN (7.8% grade 3; 0.4% grade 4), however, over half of pts experiencing grade 3/4 PN continued eribulin. Ixabepilone (IXA) is frequently used in late-line MBC pts and registration studies reported an overall PN incidence of 63% (14-21% grade 3/4). We sought to define incidence of PN of eribulin and IXA in a late-line setting since indirect comparisons suggest eribulin may have a more favorable neurotoxicity profile compared with IXA.
Methods: This randomized, two-arm, multicenter, open-label, phase II study stratified pts by pre-existing neuropathy (grade 0 or 1) and number of prior chemotherapy (CT) regimens (≥3 or &gt;3). 104 pts with locally recurrent or MBC, who had received at least one prior cytotoxic CT, including a taxane for MBC were randomized to receive eribulin mesylate (n=52; 1.4 mg/m2 2- to 5-min IV on Days 1 and 8 of a 21-day cycle) or IXA (n=52; 40 mg/m2 as a 3 h IV infusion on Day 1 of a 21-day cycle). The primary objective was to compare the incidence of neuropathic adverse events. Secondary objectives were: 1) to compare the severity of neuropathy using CTCAE grading, a patient-reported neurotoxicity questionnaire (SRNQ), and vibration sensitivity (VS); 2) to evaluate efficacy as measured by objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and progression-free survival (PFS); and 3) to evaluate safety.
Results: Of 51 eribulin and 50 IXA pts who received treatment, eribulin-treated pts experienced a trend towards less PN and treatment-emergent neuropathy (TEN) than IXA-treated pts (31.4% vs 44.0%, p=0.1632; and 33.3% vs 48.0%, p=0.1284, respectively). The incidence of grade ≥3 neuropathy was 9.8% and 22% for eribulin and IXA, respectively. Time to onset of severe neuropathy was earlier for IXA relative to eribulin (4.8 vs 9.9 weeks, respectively); by cycle 4, 44% of subjects receiving IXA experienced TEN compared with 24% on eribulin. SRNQ and VS results will be analyzed separately. Treatment-emergent adverse events (TEAEs) and serious TEAEs were comparable (98% and 96%; 37% and 34% in eribulin- and IXA-treated subjects, respectively). Eribulin-treated pts experienced less discontinuation of treatment due to neuropathy (3.9% vs 18%) or TEAEs in general (11.8% vs 32.0%) relative to IXA pts. The efficacy data for eribulin vs IXA was 15.4% vs 5.8% for ORR, 26.9% vs 19.2% for CBR, 67.3% vs 55.8% for DCR, and 104 days vs 95 days for median PFS, respectively.
Conclusions: Although the difference in overall incidence of PN and TEN was not significant for eribulin vs IXA, eribulin tended to show less PN and TEN. Eribulin also had less severe and longer time to development of grade 3/4 PN and fewer discontinuations due to toxicity.
Support: Eisai Inc.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-02.