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Pilot neoadjuvant trial in HER2 positive breast cancer with combination of nab-paclitaxel and lapatinib

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Abstract

Lapatinib, a dual kinase inhibitor against epidermal growth factor receptor (EGFR) and human epidermal receptor two (HER2) has shown efficacy in treating HER2 positive breast cancer. Nanoparticle albumin bound (nab) paclitaxel was developed to reduce toxicities from paclitaxel and improve its efficacy. Thirty patients with stage I–III HER2 positive breast cancer were treated in the neoadjuvant setting with lapatinib 1,000 mg/day and nab-paclitaxel 260 mg/m2 every 3 weeks for four cycles. The primary end point of the trial was clinical response rate (cRR) with secondary end points including pathologic complete response rate (pCR), tolerability of the combination, and marker response. The cRR was 82.8% (24 patients) with six (20.7%) patients having complete clinical response, 18 (62.1%) having partial clinical response, and five (17.2%) stable disease. A pCR was observed in five of the 28 patients (17.9%). The most frequent grade 2 toxicities were neuropathy in nine patients (30%), fatigue in seven patients (23.3%), rash in 11 patients (36.7%), and bone pain in 10 patients (33.3%). There was no significant drop in the left ventricular ejection fraction (LVEF). Of the tissue markers examined, we were not able to find a predictor of response. The combination of lapatinib and nab-paclitaxel was well tolerated and provided good efficacy in women with HER2 positive breast cancer. This combination offers an alternative non-anthracycline-containing regimen for women with HER2 positive breast cancer.

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Acknowledgments

This clinical trial (ClinicalTrials.gov ID NCT00331630) was conducted through the support of GlaxoSmithKline. Abraxis BioScience Inc. provided nab-paclitaxel. Pathology Core Facility, Robert H. Lurie Comprehensive Cancer Center, where all staining was conducted, provided the necessary support.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Northwestern University, 676 North St. Clair Street, Suite 850, Chicago, IL, 60611, USA

    Virginia G. Kaklamani, Regina Uthe, Caitlin Meservey, Mary Cianfrocca, Steven Rosen, Jamie Von Roenn & William Gradishar

  2. Department of Pathology, Northwestern University, Chicago, IL, USA

    Kalliopi Siziopikou

  3. Department of Preventive Medicine, Northwestern University, Chicago, IL, USA

    Denise Scholtens & Borko Jovanovic

  4. Department of Dermatology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Mario Lacouture

  5. Department of Dermatology, Northwestern University, Chicago, IL, USA

    Jennifer Gordon

  6. Department of Surgery, Northwestern University, Chicago, IL, USA

    Nora Hansen, Seema A. Khan, Jacqueline S. Jeruss, Kevin Bethke & Jeffrey Wayne

  7. Pathology Core Facility, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA

    Vamsi Parimi

Authors
  1. Virginia G. Kaklamani
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  2. Kalliopi Siziopikou
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  3. Denise Scholtens
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  4. Mario Lacouture
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  5. Jennifer Gordon
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  7. Caitlin Meservey
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  8. Nora Hansen
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  9. Seema A. Khan
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  10. Jacqueline S. Jeruss
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  11. Kevin Bethke
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  12. Mary Cianfrocca
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  13. Steven Rosen
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  14. Jamie Von Roenn
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  15. Jeffrey Wayne
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  16. Vamsi Parimi
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  17. Borko Jovanovic
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  18. William Gradishar
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Corresponding author

Correspondence to Virginia G. Kaklamani.

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Kaklamani, V.G., Siziopikou, K., Scholtens, D. et al. Pilot neoadjuvant trial in HER2 positive breast cancer with combination of nab-paclitaxel and lapatinib. Breast Cancer Res Treat 132, 833–842 (2012). https://doi.org/10.1007/s10549-011-1411-8

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  • DOI: https://doi.org/10.1007/s10549-011-1411-8

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