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Phase II randomized trial of weekly and every-3-week ixabepilone in metastatic breast cancer patients

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Abstract

This multicenter, open-label, randomized phase II trial compared the efficacy and tolerability of weekly ixabepilone versus the standard 3 weekly dosing regimen. Patients with human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC) were randomly assigned to receive either ixabepilone 16 mg/m2 as a 1-h intravenous (IV) infusion weekly on days 1, 8, and 15 of a 28-day cycle (1 week off therapy; n = 85), or 40 mg/m2 as a 3-h IV infusion on day 1 of a 21-day cycle (n = 91), until disease progression or unacceptable toxicity. Randomization was stratified by (i) measurable versus nonmeasurable (evaluable) disease, (ii) ≤two versus >two prior chemotherapy regimens for MBC, and (iii) hormone receptor (HR)-positive versus HR-negative breast cancer. The primary endpoint was rate of progression-free survival (PFS) at 6 months. Of 176 randomized patients, 171 were treated. The 6-month PFS rate was significantly higher in patients treated with ixabepilone every 3 weeks (42.7, 95 % confidence interval [CI] 31.5–53.5) compared with those who received ixabepilone weekly (28.6, 95 % CI 18.9–38.9; log-rank P = 0.03). Every-3-week dosing significantly prolonged median PFS versus weekly dosing (5.3 vs. 2.9 months; log-rank P = 0.05). The every-3-week regimen was associated with higher rates of grade 3/4 toxicities, particularly neutropenia (38.2 vs. 6.1 %) and a higher rate of patient withdrawal due to adverse events. These results suggest that every-3-week ixabepilone is more effective than weekly treatment in MBC, albeit with more toxicity.

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Acknowledgments

The authors thank all physicians at the participating US Oncology network sites where this study was conducted. They also thank all nurses, in particular Michelle H. Ellenwood, Marjorie Bennett, Valerie Francis, and Kirsten Stuber, who contributed to the success of this clinical trial. The authors take full responsibility for the content of this publication and confirm that it reflects their viewpoint and scientific expertise. They wish to acknowledge StemScientific, funded by Bristol-Myers Squibb, for providing writing and editorial support.

Conflict of interest

John W. Smith II, Svetislava Vukelja, Amy Rabe, Nicole Wentworth-Hartung, Nicholas Koutrelakos, Spencer H Shao, Thomas Whittaker, Yunfei Wang, and Lina Asmar declare that they have no conflict of interest. Joyce O’Shaughnessy has received remuneration from Bristol-Myers Squibb (Speakers Bureau). Diane Opatt McDowell and Pralay Mukhopadhyay are employees and stock owners of Bristol-Myers Squibb.

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Authors and Affiliations

  1. Compass Oncology, 5050 NE Hoyt Street, Suite 256, Portland, OR, 97213, USA

    John W. Smith II & Spencer H. Shao

  2. East Texas Medical Center, Clarksville, TX, USA

    Svetislava Vukelja

  3. Kansas City Cancer Center-Shawnee Mission Medical Center, Overland Park, KS, USA

    Amy Rabe

  4. Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, MN, USA

    Nicole Wentworth-Hartung

  5. Maryland Oncology Hematology, Columbia, MD, USA

    Nicholas Koutrelakos

  6. Central Indiana Cancer Centers, Anderson, IN, USA

    Thomas Whittaker

  7. McKesson Speciality Health, The Woodlands, TX, USA

    Yunfei Wang & Lina Asmar

  8. Bristol-Myers Squibb, Princeton, NJ, USA

    Diane Opatt McDowell & Pralay Mukhopadhyay

  9. Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA

    Joyce O’Shaughnessy

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  1. John W. Smith II
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Correspondence to John W. Smith II.

Additional information

Previous presentations: J. W. Smith, S. J. Vukelja, A. C. Rabe, et al. Final results of a phase II randomized trial of weekly or every-3-week ixabepilone in metastatic breast cancer (MBC). The American Society of Clinical Oncology Breast Cancer Symposium, 2010 (abstr 268).

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Smith, J.W., Vukelja, S., Rabe, A. et al. Phase II randomized trial of weekly and every-3-week ixabepilone in metastatic breast cancer patients. Breast Cancer Res Treat 142, 381–388 (2013). https://doi.org/10.1007/s10549-013-2742-4

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