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Retrospective study of the efficacy and safety of neoadjuvant docetaxel, carboplatin, trastuzumab/pertuzumab (TCH-P) in nonmetastatic HER2-positive breast cancer

Breast Cancer Research and Treatment volume 158, pages 189–193 (2016)Cite this article

Abstract

Background

Pertuzumab is FDA approved in the preoperative setting in combination with trastuzumab and chemotherapy, in women with nonmetastatic HER2 + breast cancer. The TRYPHAENA trial (n = 77) reported a pathologic complete response rate (pCR), i.e., ypT0ypN0, of 52 % in patients treated with neoadjuvant (docetaxel, carboplatin, trastuzumab, & pertuzumab) TCH-P. Aside from this study, there is limited information regarding the safety and efficacy of TCH-P in the neoadjuvant setting. Our goal was to evaluate the safety and efficacy of neoadjuvant TCH-P in a non-clinical trial setting.

Materials and methods

Cancer data registry was utilized to identify patients with HER2 + nonmetastatic breast cancer that received neoadjuvant TCH-P. pCR was defined as the absence of invasive or noninvasive cancer in breast and lymph nodes, i.e., ypT0ypN0.

Results

70 patients with a median age of 52 years met our inclusion criteria. Clinical staging was I-8.5 %; II-68.5 %; and III-22.8 %. 60 % of patients had hormone receptor (HR)-positive tumors. 23 % (16/71) of patients required dose reduction for rash, diarrhea, neuropathy, or thrombocytopenia. Overall, no patients developed grade 3–4 left ventricular systolic dysfunction(LVSD); an asymptomatic reduction in LVEF of >10 % was observed in three patients. The overall observed pCR rate was 53 %. As expected, the pCR rate was higher in patients with HR-negative breast cancer than for patients with HR+ disease: 69 % (20/29) vs. 42 % (17/41), respectively. The axillary downstaging rate was approximately 53 % (19/36).

Conclusion

Neoadjuvant TCH-P, in a nonclinical trial setting, was associated with a pCR rate of 53 % similar the reported rate in TRYPHAENA. Toxicity was manageable, with no patients experiencing symptomatic heart failure.

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References

  1. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A et al (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 12(244):707–712

    Article  Google Scholar 

  2. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182

    CAS  Article  PubMed  Google Scholar 

  3. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM et al (2013) 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 382(9897):1021–1028. doi:10.1016/S0140-6736(13)61094-61096

    CAS  Article  PubMed  Google Scholar 

  4. Nahta R, Hung MC, Esteva FJ (2004) The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Res 64:2343–2346

    CAS  Article  PubMed  Google Scholar 

  5. Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M (2009) Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res 69:9330–9336

    CAS  Article  PubMed  Google Scholar 

  6. Swain SM, Baselga J et al (2015) Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 372:724–734

    CAS  Article  PubMed  Google Scholar 

  7. Gianni L, Pienkowski T, Im YH, Roman L et al (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13(1):25–32. doi:10.1016/S1470-2045(11)70336-9 Epub 2011 Dec 6

    CAS  Article  PubMed  Google Scholar 

  8. Cortazar P, Zhang L, Untch M et al (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384:164–172

    Article  PubMed  Google Scholar 

  9. de Azambuja E, Holmes AP et al (2014) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol 15:1137–1146

    Article  PubMed  Google Scholar 

  10. Romond EH, Jeong JH, Rastogi P et al (2012) Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 30:3792–3799

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Slamon D, Eiermann W, Robert N et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Schneeweiss A et al (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24:2278–2284

    CAS  Article  PubMed  Google Scholar 

  13. Wolff Antonio C et al (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. J Clin Oncol 31(31):3997–4013

    Article  PubMed  Google Scholar 

  14. Minckwitz Von et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 30(15):1796–1804

    Article  Google Scholar 

  15. Cortazar P et al (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384(9938):164–172

    Article  PubMed  Google Scholar 

  16. Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0, June 2010, National Institutes of Health, National Cancer Institute. http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf

  17. Baselga J, Bradbury I, Eidtmann H et al (2012) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 379:633–640

    CAS  Article  PubMed  Google Scholar 

  18. Guarneri V, Frassoldati A, Bottini A et al (2012) Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study. J Clin Oncol 30:1989–1995

    CAS  Article  PubMed  Google Scholar 

  19. Robidoux A, Tang G, Rastogi P et al (2012) Evaluation of lapatinib as a component of neoadjuvant therapy for HER2+ operable breast cancer: NSABP protocol B-41. J Clin Oncol 30(18 Suppl):506

    Google Scholar 

  20. Dang C, Guo H, Najita J et al (2015) Cardiac outcomes of patients receiving adjuvant weekly paclitaxel and trastuzumab for node-negative, ERBB2-positive breast cancer. JAMA Oncol

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Affiliations

  1. Department of Hematology Oncology, Cleveland Clinic Taussig Cancer Institute, Mail Code R35, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Shruti R. Tiwari, Paola Raska, Jame Abraham, Halle Moore, G. Thomas Budd & Alberto J. Montero

  2. Department of Medicine, University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, OH, 44106, USA

    Prasun Mishra

  3. Department of Anatomic Pathology, Cleveland Clinic Main Campus, Mail Code L25, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Benjamin Calhoun

  4. Department of General Surgery/Breast Services, Cleveland Clinic Main Campus, Mail Code A81, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Alicia Fanning, Stephanie Valente, Robyn Stewart & Stephen R. Grobmyer

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  1. Shruti R. Tiwari
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  2. Prasun Mishra
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  3. Paola Raska
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  5. Jame Abraham
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  6. Halle Moore
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  7. G. Thomas Budd
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Corresponding author

Correspondence to Alberto J. Montero.

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Conflict of interest

The authors declare there is no conflict of interest in the writing, preparing, or finalizing of this manuscript. All authors have no disclosures other than GT Budd who has research funding from Genentech/Roche.

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Tiwari, S.R., Mishra, P., Raska, P. et al. Retrospective study of the efficacy and safety of neoadjuvant docetaxel, carboplatin, trastuzumab/pertuzumab (TCH-P) in nonmetastatic HER2-positive breast cancer. Breast Cancer Res Treat 158, 189–193 (2016). https://doi.org/10.1007/s10549-016-3866-0

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  • DOI: https://doi.org/10.1007/s10549-016-3866-0

Keywords

  • HER 2 positive
  • Neoadjuvant therapy
  • Pathologic complete response
  • Pertuzumab
  • Breast cancer