Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes

Gabriel N. Hortobagyi; Henry L. Gomez; Rubi K. Li; Hyun Cheol Chung; Luis E. Fein; Valorie F. Chan; Jacek Jassem; Guillermo L. Lerzo; Xavier B. Pivot; Fernando Hurtado De Mendoza; Binghe Xu; Linda T. Vahdat; Ronald A. Peck; Pralay Mukhopadhyay; Henri H. Roché

doi:10.1007/s10549-010-0901-4

Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes

Gabriel N. Hortobagyi, Henry L. Gomez, Rubi K. Li, Hyun Cheol Chung, Luis E. Fein, Valorie F. Chan, Jacek Jassem, Guillermo L. Lerzo, Xavier B. Pivot, Fernando Hurtado De Mendoza, Binghe Xu, Linda T. Vahdat, Ronald A. Peck, Pralay Mukhopadhyay, Henri H. Roché

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

63 Citations (Scopus)

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/m² 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/m² 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 (ClinicalTrials.gov number, NCT000080301).

Original language	English
Pages (from-to)	409-418
Number of pages	10
Journal	Breast Cancer Research and Treatment
Volume	122
Issue number	2
DOIs	https://doi.org/10.1007/s10549-010-0901-4
Publication status	Published - 2010 Jul

Bibliographical note

Funding Information:
Acknowledgments CA163-046 was funded by Bristol-Myers Squibb. The authors wish to thank the patients and all the investigators who participated in the study. Professional medical writing and editorial assistance provided by Ananya Bhattacharya, employee of Bristol-Myers Squibb. The authors vouch for the completeness and accuracy of results presented.

Funding Information:
Conflict of interest statement GH has served as a consultant for Bristol-Myers Squibb and Novartis and has a commercial research grant from Novartis; LF has served as a consultant for Bristol-Myers Squibb; VC has received honoraria from Eli Lilly and Novartis and has served as a consultant for Astra Zeneca; JJ has served as a consultant for Bristol-Myers Squibb and Glaxo SmithKleine; XP has received honoraria from Roche, Glaxo SmithKleine, and Novartis, has served as a consultant for Roche and has received commercial research support from Roche; LV has received honoraria from Bristol-Myers Squibb, commercial research grant from Bristol-Myers Squibb, Curagen, Imclone, and Glaxo SmithKleine, and has served as a consultant for Bristol-Myers Squibb, Bayer, and Onyx; HG, RKL, HCC GL, FM BX, and HR have no financial relationships to disclose; RP and PM are employees of Bristol-Myers Squibb.

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10549-010-0901-4

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Hortobagyi, G. N., Gomez, H. L., Li, R. K., Chung, H. C., Fein, L. E., Chan, V. F., Jassem, J., Lerzo, G. L., Pivot, X. B., De Mendoza, F. H., Xu, B., Vahdat, L. T., Peck, R. A., Mukhopadhyay, P., & Roché, H. H. (2010). Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes. Breast Cancer Research and Treatment, 122(2), 409-418. https://doi.org/10.1007/s10549-010-0901-4

Hortobagyi, Gabriel N. ; Gomez, Henry L. ; Li, Rubi K. ; Chung, Hyun Cheol ; Fein, Luis E. ; Chan, Valorie F. ; Jassem, Jacek ; Lerzo, Guillermo L. ; Pivot, Xavier B. ; De Mendoza, Fernando Hurtado ; Xu, Binghe ; Vahdat, Linda T. ; Peck, Ronald A. ; Mukhopadhyay, Pralay ; Roché, Henri H. / Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes. In: Breast Cancer Research and Treatment. 2010 ; Vol. 122, No. 2. pp. 409-418.

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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/m2 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/m2 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 (ClinicalTrials.gov number, NCT000080301).",

author = "Hortobagyi, {Gabriel N.} and Gomez, {Henry L.} and Li, {Rubi K.} and Chung, {Hyun Cheol} and Fein, {Luis E.} and Chan, {Valorie F.} and Jacek Jassem and Lerzo, {Guillermo L.} and Pivot, {Xavier B.} and {De Mendoza}, {Fernando Hurtado} and Binghe Xu and Vahdat, {Linda T.} and Peck, {Ronald A.} and Pralay Mukhopadhyay and Roch{\'e}, {Henri H.}",

note = "Funding Information: Acknowledgments CA163-046 was funded by Bristol-Myers Squibb. The authors wish to thank the patients and all the investigators who participated in the study. Professional medical writing and editorial assistance provided by Ananya Bhattacharya, employee of Bristol-Myers Squibb. The authors vouch for the completeness and accuracy of results presented. Funding Information: Conflict of interest statement GH has served as a consultant for Bristol-Myers Squibb and Novartis and has a commercial research grant from Novartis; LF has served as a consultant for Bristol-Myers Squibb; VC has received honoraria from Eli Lilly and Novartis and has served as a consultant for Astra Zeneca; JJ has served as a consultant for Bristol-Myers Squibb and Glaxo SmithKleine; XP has received honoraria from Roche, Glaxo SmithKleine, and Novartis, has served as a consultant for Roche and has received commercial research support from Roche; LV has received honoraria from Bristol-Myers Squibb, commercial research grant from Bristol-Myers Squibb, Curagen, Imclone, and Glaxo SmithKleine, and has served as a consultant for Bristol-Myers Squibb, Bayer, and Onyx; HG, RKL, HCC GL, FM BX, and HR have no financial relationships to disclose; RP and PM are employees of Bristol-Myers Squibb.",

year = "2010",

month = jul,

doi = "10.1007/s10549-010-0901-4",

language = "English",

volume = "122",

pages = "409--418",

journal = "Breast Cancer Research and Treatment",

issn = "0167-6806",

publisher = "Springer New York",

number = "2",

}

Hortobagyi, GN, Gomez, HL, Li, RK, Chung, HC, Fein, LE, Chan, VF, Jassem, J, Lerzo, GL, Pivot, XB, De Mendoza, FH, Xu, B, Vahdat, LT, Peck, RA, Mukhopadhyay, P & Roché, HH 2010, 'Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes', Breast Cancer Research and Treatment, vol. 122, no. 2, pp. 409-418. https://doi.org/10.1007/s10549-010-0901-4

Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes. / Hortobagyi, Gabriel N.; Gomez, Henry L.; Li, Rubi K.; Chung, Hyun Cheol; Fein, Luis E.; Chan, Valorie F.; Jassem, Jacek; Lerzo, Guillermo L.; Pivot, Xavier B.; De Mendoza, Fernando Hurtado; Xu, Binghe; Vahdat, Linda T.; Peck, Ronald A.; Mukhopadhyay, Pralay; Roché, Henri H.

In: Breast Cancer Research and Treatment, Vol. 122, No. 2, 07.2010, p. 409-418.

Research output: Contribution to journal › Article › peer-review

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T1 - Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes

AU - Hortobagyi, Gabriel N.

AU - Gomez, Henry L.

AU - Li, Rubi K.

AU - Chung, Hyun Cheol

AU - Fein, Luis E.

AU - Chan, Valorie F.

AU - Jassem, Jacek

AU - Lerzo, Guillermo L.

AU - Pivot, Xavier B.

AU - De Mendoza, Fernando Hurtado

AU - Xu, Binghe

AU - Vahdat, Linda T.

AU - Peck, Ronald A.

AU - Mukhopadhyay, Pralay

AU - Roché, Henri H.

N1 - Funding Information: Acknowledgments CA163-046 was funded by Bristol-Myers Squibb. The authors wish to thank the patients and all the investigators who participated in the study. Professional medical writing and editorial assistance provided by Ananya Bhattacharya, employee of Bristol-Myers Squibb. The authors vouch for the completeness and accuracy of results presented. Funding Information: Conflict of interest statement GH has served as a consultant for Bristol-Myers Squibb and Novartis and has a commercial research grant from Novartis; LF has served as a consultant for Bristol-Myers Squibb; VC has received honoraria from Eli Lilly and Novartis and has served as a consultant for Astra Zeneca; JJ has served as a consultant for Bristol-Myers Squibb and Glaxo SmithKleine; XP has received honoraria from Roche, Glaxo SmithKleine, and Novartis, has served as a consultant for Roche and has received commercial research support from Roche; LV has received honoraria from Bristol-Myers Squibb, commercial research grant from Bristol-Myers Squibb, Curagen, Imclone, and Glaxo SmithKleine, and has served as a consultant for Bristol-Myers Squibb, Bayer, and Onyx; HG, RKL, HCC GL, FM BX, and HR have no financial relationships to disclose; RP and PM are employees of Bristol-Myers Squibb.

PY - 2010/7

Y1 - 2010/7

N2 - 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/m2 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/m2 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 (ClinicalTrials.gov number, NCT000080301).

AB - 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/m2 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/m2 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 (ClinicalTrials.gov number, NCT000080301).

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Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes

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Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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