Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer

Eva Thomas, Josep Tabernero, Monica Fornier, Pierfranco Conté, Pierre Fumoleau, Ana Lluch, Linda T. Vahdat, Craig A. Bunnell, Howard A. Burris, Patrice Viens, José Baselga, Edgardo Rivera, Valentina Guarneri, Valerie Poulart, Judith Klimovsky, David Lebwohl, Miguel Martin

Research output: Contribution to journalArticle

255 Citations (Scopus)

Abstract

Purpose: Ixabepilone (BMS-247550) is an epothilone analog that optimizes the properties of naturally occurring epothilone B. Natural epothilones and their analogs promote tumor cell death by binding to tubulin and stabilizing microtubules, causing apoptosis. This international phase II trial assessed the activity of ixabepilone in patients with metastatic breast cancer (MBC) that was resistant to taxane therapy. Patients and Methods: MBC patients, who had experienced disease progression while receiving or within 4 months of taxane therapy (6 months if adjuvant taxane only), and who had a taxane as their last regimen, received ixabepilone (1- or 3-hour infusion of 50 mg/m2 or 3-hour infusion of 40 mg/m2 every 3 weeks). Results: Of 49 patients treated with 40 mg/m2 ixabepilone during 3 hours, 35 (73%) had experienced disease progression within 1 month of their last taxane dose. The response rate was 12% (95% CI, 4.7% to 26.5%). All responses (n = 6) were partial; five of six patients had not responded to prior taxane therapy. In responders, the median response duration was 10.4 months. In 20 patients (41%), stable disease was the best outcome. Median time to progression was 2.2 months (95% CI, 1.4 to 3.2 months); median survival was 7.9 months. For treated patients across all cohorts (intent-to-treat population), the response rate was also 12% (eight of 66). Treatment-related adverse events in the study were manageable and primarily grade 1/2. Treatment-related neuropathy was mostly sensory and mild to moderate. Conclusion: Ixabepilone (40 mg/m2 as a 3-hour infusion every 3 weeks) demonstrates promising antitumor activity and an acceptable safety profile in patients with taxane-resistant MBC.

Original languageEnglish
Pages (from-to)3399-3406
Number of pages8
JournalJournal of Clinical Oncology
Volume25
Issue number23
DOIs
Publication statusPublished - Aug 10 2007

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Phase II Clinical Trials
Breast Neoplasms
Epothilones
Disease Progression
Therapeutics
epothilone B
taxane
ixabepilone
Tubulin
Microtubules
Cell Death
Apoptosis
Safety
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer. / Thomas, Eva; Tabernero, Josep; Fornier, Monica; Conté, Pierfranco; Fumoleau, Pierre; Lluch, Ana; Vahdat, Linda T.; Bunnell, Craig A.; Burris, Howard A.; Viens, Patrice; Baselga, José; Rivera, Edgardo; Guarneri, Valentina; Poulart, Valerie; Klimovsky, Judith; Lebwohl, David; Martin, Miguel.

In: Journal of Clinical Oncology, Vol. 25, No. 23, 10.08.2007, p. 3399-3406.

Research output: Contribution to journalArticle

Thomas, E, Tabernero, J, Fornier, M, Conté, P, Fumoleau, P, Lluch, A, Vahdat, LT, Bunnell, CA, Burris, HA, Viens, P, Baselga, J, Rivera, E, Guarneri, V, Poulart, V, Klimovsky, J, Lebwohl, D & Martin, M 2007, 'Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer', Journal of Clinical Oncology, vol. 25, no. 23, pp. 3399-3406. https://doi.org/10.1200/JCO.2006.08.9102
Thomas, Eva ; Tabernero, Josep ; Fornier, Monica ; Conté, Pierfranco ; Fumoleau, Pierre ; Lluch, Ana ; Vahdat, Linda T. ; Bunnell, Craig A. ; Burris, Howard A. ; Viens, Patrice ; Baselga, José ; Rivera, Edgardo ; Guarneri, Valentina ; Poulart, Valerie ; Klimovsky, Judith ; Lebwohl, David ; Martin, Miguel. / Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 23. pp. 3399-3406.
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abstract = "Purpose: Ixabepilone (BMS-247550) is an epothilone analog that optimizes the properties of naturally occurring epothilone B. Natural epothilones and their analogs promote tumor cell death by binding to tubulin and stabilizing microtubules, causing apoptosis. This international phase II trial assessed the activity of ixabepilone in patients with metastatic breast cancer (MBC) that was resistant to taxane therapy. Patients and Methods: MBC patients, who had experienced disease progression while receiving or within 4 months of taxane therapy (6 months if adjuvant taxane only), and who had a taxane as their last regimen, received ixabepilone (1- or 3-hour infusion of 50 mg/m2 or 3-hour infusion of 40 mg/m2 every 3 weeks). Results: Of 49 patients treated with 40 mg/m2 ixabepilone during 3 hours, 35 (73{\%}) had experienced disease progression within 1 month of their last taxane dose. The response rate was 12{\%} (95{\%} CI, 4.7{\%} to 26.5{\%}). All responses (n = 6) were partial; five of six patients had not responded to prior taxane therapy. In responders, the median response duration was 10.4 months. In 20 patients (41{\%}), stable disease was the best outcome. Median time to progression was 2.2 months (95{\%} CI, 1.4 to 3.2 months); median survival was 7.9 months. For treated patients across all cohorts (intent-to-treat population), the response rate was also 12{\%} (eight of 66). Treatment-related adverse events in the study were manageable and primarily grade 1/2. Treatment-related neuropathy was mostly sensory and mild to moderate. Conclusion: Ixabepilone (40 mg/m2 as a 3-hour infusion every 3 weeks) demonstrates promising antitumor activity and an acceptable safety profile in patients with taxane-resistant MBC.",
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T1 - Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer

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AU - Tabernero, Josep

AU - Fornier, Monica

AU - Conté, Pierfranco

AU - Fumoleau, Pierre

AU - Lluch, Ana

AU - Vahdat, Linda T.

AU - Bunnell, Craig A.

AU - Burris, Howard A.

AU - Viens, Patrice

AU - Baselga, José

AU - Rivera, Edgardo

AU - Guarneri, Valentina

AU - Poulart, Valerie

AU - Klimovsky, Judith

AU - Lebwohl, David

AU - Martin, Miguel

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N2 - Purpose: Ixabepilone (BMS-247550) is an epothilone analog that optimizes the properties of naturally occurring epothilone B. Natural epothilones and their analogs promote tumor cell death by binding to tubulin and stabilizing microtubules, causing apoptosis. This international phase II trial assessed the activity of ixabepilone in patients with metastatic breast cancer (MBC) that was resistant to taxane therapy. Patients and Methods: MBC patients, who had experienced disease progression while receiving or within 4 months of taxane therapy (6 months if adjuvant taxane only), and who had a taxane as their last regimen, received ixabepilone (1- or 3-hour infusion of 50 mg/m2 or 3-hour infusion of 40 mg/m2 every 3 weeks). Results: Of 49 patients treated with 40 mg/m2 ixabepilone during 3 hours, 35 (73%) had experienced disease progression within 1 month of their last taxane dose. The response rate was 12% (95% CI, 4.7% to 26.5%). All responses (n = 6) were partial; five of six patients had not responded to prior taxane therapy. In responders, the median response duration was 10.4 months. In 20 patients (41%), stable disease was the best outcome. Median time to progression was 2.2 months (95% CI, 1.4 to 3.2 months); median survival was 7.9 months. For treated patients across all cohorts (intent-to-treat population), the response rate was also 12% (eight of 66). Treatment-related adverse events in the study were manageable and primarily grade 1/2. Treatment-related neuropathy was mostly sensory and mild to moderate. Conclusion: Ixabepilone (40 mg/m2 as a 3-hour infusion every 3 weeks) demonstrates promising antitumor activity and an acceptable safety profile in patients with taxane-resistant MBC.

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