title: Eribulin mesylate versus ixabepilone in patients with metastatic breast cancer: a randomized Phase II study comparing the incidence of peripheral neuropathy.
abstract: Peripheral neuropathy is a common toxicity associated with tubulin-targeted chemotherapeutic agents. This Phase II study compares the incidence and severity of neuropathy associated with eribulin mesylate or ixabepilone in metastatic breast cancer (MBC). The primary objective was to assess the incidence of neuropathy; the study was designed to detect a difference in neuropathy rate of 35 % for eribulin versus 63 % for ixabepilone (odds ratio 0.316, 80 % power, 0.05 two-sided significance level). Eligibility criteria included: MBC; prior taxane therapy; at least one chemotherapy for advanced disease; no or minimal pre-existing neuropathy (Grade 0 or 1). The intent-to-treat population comprised 104 patients randomized (1:1) to eribulin mesylate (1.4 mg/m(2), 2-5 min intravenous on days 1 and 8) or ixabepilone (40 mg/m(2), 3 h intravenous on day 1) on a 21-day cycle. 101 patients in the safety population received a median of 5.0 eribulin and 3.5 ixabepilone cycles. Incidence of neuropathy (any grade) was 33.3 and 48.0 %, and peripheral neuropathy was 31.4 and 44.0 % for eribulin and ixabepilone, respectively. After controlling for pre-existing neuropathy and number of prior chemotherapies, these differences were not significant. Compared with ixabepilone, fewer patients receiving eribulin discontinued treatment due to neuropathy (3.9 vs. 18.0 %) or adverse events (AEs) in general (11.8 vs. 32.0 %). Time to onset of neuropathy was 35.9 weeks for eribulin and 11.6 weeks for ixabepilone, and time to resolution was 48 versus 10 weeks, respectively; other AEs were comparable. Objective responses were 15.4 versus 5.8 % and clinical benefit rates were 26.9 versus 19.2 %. In conclusion, after controlling for pre-existing neuropathy and number of prior chemotherapies, the differences in the incidence of neuropathy with eribulin and ixabepilone were not statistically significant. Onset of neuropathy tended to occur later with eribulin and resolve later.
authors.affiliation: Weill Cornell Medical College, 425 East 61st Street, 8th Floor, New York, NY 10065, USA. ltv2001@med.cornell.edu
authors.forename: Linda T
authors.initials: LT
authors.lastname: Vahdat
authors.forename: Agustin A
authors.initials: AA
authors.lastname: Garcia
authors.forename: Charles
authors.initials: C
authors.lastname: Vogel
authors.forename: Christine
authors.initials: C
authors.lastname: Pellegrino
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Lindquist
authors.forename: Nicholas
authors.initials: N
authors.lastname: Iannotti
authors.forename: Prashanth
authors.initials: P
authors.lastname: Gopalakrishna
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D034261:Epothilones / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005663:Furans / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007659:Ketones / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D015996:Survival Rate; D000095662:Polyether Polyketides
chemical_list: D034261:Epothilones; D005663:Furans; D007659:Ketones; C430592:ixabepilone; C490954:eribulin; D000095662:Polyether Polyketides