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A phase II trial of ixabepilone and cyclophosphamide as neoadjuvant therapy for patients with HER2-negative breast cancer: correlation of pathologic complete response with the 21-gene recurrence score

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Abstract

Ixabepilone and the taxanes have similar activity in the first-line treatment of metastatic breast cancer, and ixabepilone is sometimes effective in taxane-refractory patients. We conducted a phase 2 trial to evaluate ixabepilone in combination with cyclophosphamide as neoadjuvant treatment for patients with locally advanced HER2-negative breast cancer. Response to neoadjuvant treatment was correlated with the baseline 21-gene Recurrence Score® (Oncotype DX; Genomic Health Inc, Redwood City, CA). Eligible women with HER2-negative locally advanced breast cancer received ixabepilone 40 mg/m2 plus cyclophosphamide 600 mg/m2 on day 1 of each 21-day cycle. Following 6 cycles, patients underwent definitive surgery. Primary endpoint was rate of pathologic complete response (pCR). Breast biopsy tumor samples were obtained at pretreatment and at surgery in patients with residual disease. Tumor specimens were analyzed using the 21-gene assay. One hundred sixty-eight patients (median age 52 years; 45 % triple-negative) were enrolled; 161 (96 %) underwent definitive surgery following neoadjuvant ixabepilone/cyclophosphamide. Overall, 27 patients (17 %) achieved pCR, including 19 of 73 (26 %) triple-negative patients. The most frequently occurring grade 3/4 toxicity was neutropenia (98 patients; 58 %). Recurrence Scores were highly correlated with achievement of pCR (0/36 with low or intermediate Recurrence Scores vs. 19/72 with high Recurrence Scores; p = 0.002). There was high concordance between baseline and post-treatment Recurrence Scores in the 72 patients with paired samples. The combination of ixabepilone and cyclophosphamide yielded a pCR rate of 17 %, similar to other neoadjuvant chemotherapy regimens. Pathologic complete responses occurred only in patients with high-risk baseline Recurrence Scores.

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Acknowledgments

This study was supported in part by Grants from Bristol-Myer Squibb and Genomic Health, Inc.

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Authors and Affiliations

  1. Sarah Cannon Research Institute, 3322 West End Ave., Suite 900, Nashville, TN, 37203, USA

    Denise A. Yardley, Nancy W. Peacock, Mythili Shastry, Howard A. Burris III & John D. Hainsworth

  2. Tennessee Oncology, PLLC, Nashville, TN, USA

    Denise A. Yardley, Nancy W. Peacock, Howard A. Burris III & John D. Hainsworth

  3. Oncology Hematology Care, Inc, Cincinnati, OH, USA

    Rebecca G. Bechhold

  4. Center for Breast Health, Bethesda, MD, USA

    Carolyn B. Hendricks

  5. Genomic Health, Inc, Redwood City, CA, USA

    Carl N. Yoshizawa & Amy P. Sing

Authors
  1. Denise A. Yardley
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  2. Nancy W. Peacock
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  3. Mythili Shastry
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  4. Howard A. Burris III
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  5. Rebecca G. Bechhold
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  6. Carolyn B. Hendricks
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  7. Carl N. Yoshizawa
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  8. Amy P. Sing
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  9. John D. Hainsworth
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Corresponding author

Correspondence to John D. Hainsworth.

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Conflict of interest

C. N. Yoshizawa and A. P. Sing are employees and own stock of Genomic Health, Inc. All other authors declare that they have no conflict of interests.

Additional information

Clinical Trial Registration Number: Clinicaltrials.gov, NCT00866905 http://clinicaltrials.gov/ct2/show/NCT00866905.

Appendix: Sarah Cannon Oncology Research Consortium participating sites

Appendix: Sarah Cannon Oncology Research Consortium participating sites

Tennessee Oncology, PLLC

Nashville, TN

Tennessee Oncology—Chattanooga

Chattanooga, TN

Florida Cancer Specialists

Fort Myers, FL

Virginia Cancer Institute

Richmond, VA

South Carolina Oncology Associates

Columbia, SC

Oncology Hematology Care

Cincinnati, OH

Center for Cancer and Blood Disorders

Bethesda, MD

Northeast Georgia Medical Center

Gainesville, GA

South Texas Oncology & Hematology

San Antonio, TX

Nebraska Methodist Cancer Center

Omaha, NE

Watson Clinic for Cancer Research

Lakeland, FL

Mercy Hospital

Portland, ME

St. Louis Cancer Care

Bridgeton, MO

Family Cancer Center Foundation

Memphis, TN

Providence Medical Group

Terre Haute, IN

Aventura Medical Center

Aventura, FL

Cancer Centers of Southwest Oklahoma Research

Lawton, OK

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Yardley, D.A., Peacock, N.W., Shastry, M. et al. A phase II trial of ixabepilone and cyclophosphamide as neoadjuvant therapy for patients with HER2-negative breast cancer: correlation of pathologic complete response with the 21-gene recurrence score. Breast Cancer Res Treat 154, 299–308 (2015). https://doi.org/10.1007/s10549-015-3613-y

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  • DOI: https://doi.org/10.1007/s10549-015-3613-y

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