title: Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes.
abstract: Limited proven treatment options exist for patients with metastatic breast cancer (MBC) resistant to anthracycline and taxane treatment. Ixabepilone, a novel semisynthetic analog of epothilone B, has demonstrated single-agent activity in MBC resistant to anthracyclines and taxanes. In combination with capecitabine in a phase III trial (CA163-046) in this setting, ixabepilone prolonged progression-free survival and increased objective response rate relative to capecitabine (Thomas et al. J Clin Oncol 25:5210-5217, 2007). Here, we report the results of overall survival (OS), a secondary efficacy endpoint from the CA163-046 trial. Seven hundred fifty-two patients with MBC resistant to anthracyclines and taxanes were randomized to ixabepilone (40 mg/m(2) intravenously on day 1 of a 21-day cycle) plus capecitabine (2,000 mg/m(2) orally on days 1 through 14 of a 21-day cycle) or capecitabine alone (2,500 mg/m(2) on the same schedule). Patients receiving ixabepilone plus capecitabine treatment had a median survival of 12.9 months compared to 11.1 months for patients receiving capecitabine alone (HR = 0.9; 95%CI: 077-1.05; P = 0.19). This observed increase in median OS favored the combination; however, the difference was not statistically significant. Predefined subset analyses showed a clinically meaningful increase in OS in KPS 70-80 patients receiving ixabepilone plus capecitabine (HR = 0.75; 95% CI: 0.58-0.98). Ixabepilone plus capecitabine did not show a significant improvement in survival compared to capecitabine alone in patients with MBC resistant to anthracyclines and taxanes. The observed differences in survival favored the combination arm. A clinical benefit was also seen in patients in the KPS 70-80 subgroup.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1354, Houston, TX 77030-4009, USA. ghortoba@mdanderson.com
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Henry L
authors.initials: HL
authors.lastname: Gomez
authors.forename: Rubi K
authors.initials: RK
authors.lastname: Li
authors.forename: Hyun-Cheol
authors.initials: HC
authors.lastname: Chung
authors.forename: Luis E
authors.initials: LE
authors.lastname: Fein
authors.forename: Valorie F
authors.initials: VF
authors.lastname: Chan
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.forename: Guillermo L
authors.initials: GL
authors.lastname: Lerzo
authors.forename: Xavier B
authors.initials: XB
authors.lastname: Pivot
authors.forename: Fernando
authors.initials: F
authors.lastname: Hurtado de Mendoza
authors.forename: Binghe
authors.initials: B
authors.lastname: Xu
authors.forename: Linda T
authors.initials: LT
authors.lastname: Vahdat
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Peck
authors.forename: Pralay
authors.initials: P
authors.lastname: Mukhopadhyay
authors.forename: Henri H
authors.initials: HH
authors.lastname: Roché
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001208:Asia; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000556:secondary; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000008:administration & dosage; D005060:Europe; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013020:South America; D043823:Taxoids / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000008:administration & dosage; D014481:United States
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D034261:Epothilones; D043823:Taxoids; D050257:Tubulin Modulators; D003841:Deoxycytidine; D000069287:Capecitabine; C430592:ixabepilone; D005472:Fluorouracil