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Clinical Trial
. 2010 Jul 10;28(20):3256-63.
doi: 10.1200/JCO.2009.24.4244. Epub 2010 Jun 7.

Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane

Joseph A Sparano  1 , Eduard Vrdoljak, Oliver Rixe, Binghe Xu, Alexey Manikhas, Carlos Medina, Susanne Crocamo Ventilari Da Costa, Jungsil Ro, Gonzalo Rubio, Monica Rondinon, Gumersindo Perez Manga, Ronald Peck, Valerie Poulart, Pierfranco Conte
Affiliations
Clinical Trial

Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane

Joseph A Sparano et al. J Clin Oncol. .

Abstract

Purpose: 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.

Patients and 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.

Conclusion: 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.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT flowchart for CA163-048.
Fig 2.
Fig 2.
(A) Overall survival (OS) Kaplan-Meier curves. OS distribution for the treatment arms receiving ixabepilone combination (I + C) versus capecitabine alone (C) are shown. (B) OS hazard ratio (HR) and 95% CI for subset analyses. HRs less than 1 favor combination therapy. KPS, Karnofsky performance status; Mod, moderate; Sev, severe; chemo, chemotherapy; HER2, human epidermal growth factor receptor 2; ER, estrogen receptor; PR, progesterone receptor.
Fig 3.
Fig 3.
(A) Investigator review of the progression-free survival (PFS) Kaplan-Meier curves. PFS distribution for patients with measurable disease receiving ixabepilone combination (I + C) versus capecitabine alone (C) are shown. (B) PFS hazard ratio (HR) and 95% CI for subset analyses. HRs less than 1 favor combination therapy. KPS, Karnofsky performance status; Mod, moderate; Sev, severe; chemo, chemotherapy; HER2, human epidermal growth factor receptor 2; ER, estrogen receptor; PR, progesterone receptor.
Fig 4.
Fig 4.
Time to resolution of grade 3 to 4 ixabepilone-related peripheral neuropathy to baseline or grade 1. Resolution was defined as return of symptoms to baseline or grade 1. Analysis included 120 ixabepilone-treated patients with peripheral neuropathy that occurred within 30 days of the last dose of ixabepilone and had a median resolution time of 6.2 weeks.
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