Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane.
OBJECTIVE
We sought to determine whether the combination of ixabepilone plus capecitabine improved overall survival (OS) compared with capecitabine alone in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes.


METHODS
A total of 1,221 patients with MBC previously treated with anthracycline and taxanes were randomly assigned to ixabepilone (40 mg/m(2) intravenously on day 1) plus capecitabine (2,000 mg/m(2) orally on days 1 through 14) or capecitabine alone (2,500 mg/m(2) on the same schedule) given every 21 days. The trial was powered to detect a 20% reduction in the hazard ratio (HR) for death.


RESULTS
There was no significant difference in OS between the combination and capecitabine monotherapy arm, the primary end point (median, 16.4 v 15.6 months; HR = 0.9; 95% CI, 078 to 1.03; P = .1162). The arms were well balanced with the exception of a higher prevalence of impaired performance status (Karnofsky performance status 70% to 80%) in the combination arm (32% v 25%). In a secondary Cox regression analysis adjusted for performance status and other prognostic factors, OS was improved for the combination (HR = 0.85; 95% CI, 0.75 to 0.98; P = .0231). In 79% of patients with measurable disease, the combination significantly improved progression-free survival (PFS; median, 6.2 v 4.2 months; HR = 0.79; P = .0005) and response rate (43% v 29%; P < .0001). Grade 3 to 4 neuropathy occurred in 24% treated with the combination, but was reversible.


CONCLUSIONS
This study confirmed a previous trial demonstrating improved PFS and response for the ixabepilone-capecitabine combination compared with capecitabine alone, although this did not result in improved survival.
Sparano
Joseph A
JA
Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. jsparano@montefiore.org
Vrdoljak
Eduard
E
Rixe
Oliver
O
Xu
Binghe
B
Manikhas
Alexey
A
Medina
Carlos
C
Da Costa
Susanne Crocamo Ventilari
SC
Ro
Jungsil
J
Rubio
Gonzalo
G
Rondinon
Monica
M
Perez Manga
Gumersindo
G
Peck
Ronald
R
Poulart
Valerie
V
Conte
Pierfranco
P
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D034261:Epothilones / Q000008:administration & dosage*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D019233:Retreatment; D043823:Taxoids / Q000008:administration & dosage
D018943:Anthracyclines; D034261:Epothilones; D043823:Taxoids; D003841:Deoxycytidine; D000069287:Capecitabine; C430592:ixabepilone; D005472:Fluorouracil