Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes.
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.
Hortobagyi
Gabriel N
GN
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
Gomez
Henry L
HL
Li
Rubi K
RK
Chung
Hyun-Cheol
HC
Fein
Luis E
LE
Chan
Valorie F
VF
Jassem
Jacek
J
Lerzo
Guillermo L
GL
Pivot
Xavier B
XB
Hurtado de Mendoza
Fernando
F
Xu
Binghe
B
Vahdat
Linda T
LT
Peck
Ronald A
RA
Mukhopadhyay
Pralay
P
Roché
Henri H
HH
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
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D034261:Epothilones; D043823:Taxoids; D050257:Tubulin Modulators; D003841:Deoxycytidine; D000069287:Capecitabine; C430592:ixabepilone; D005472:Fluorouracil