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Effectiveness and tolerability of neoadjuvant pertuzumab-containing regimens for HER2-positive localized breast cancer

  • Laura Spring
  • Andrzej Niemierko
  • Stephanie Haddad
  • Megan Yuen
  • Amy Comander
  • Kerry Reynolds
  • Jennifer Shin
  • Atul Bahn
  • Elena Brachtel
  • Michelle Specht
  • Barbara L. Smith
  • Alphonse Taghian
  • Rachel Jimenez
  • Jeffrey Peppercorn
  • Steven J. Isakoff
  • Beverly Moy
  • Aditya Bardia
Brief Report
  • 46 Downloads

Abstract

Purpose

Based on improvement in pathologic complete response (pCR) in the NeoSphere and TRYPHAENA studies, the FDA approved neoadjuvant pertuzumab for HER2+ localized breast cancer. These studies demonstrated high pCR rates with THP (docetaxel + HP), FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-THP, and TCHP (docetaxel, carboplatin + HP). However, in the United States, doxorubicin/cyclophosphamide (AC) is favored over FEC despite no data comparing neoadjuvant AC-THP with AC-TH or TCHP. Here we report outcomes for patients with localized HER2+ breast cancer treated with pertuzumab-containing neoadjuvant regimens and AC-TH.

Methods

We reviewed clinicopathological characteristics of patients with HER2+ breast cancer (Stage I–III) treated with either a neoadjuvant pertuzumab-containing regimen or dose-dense (dd) AC-TH, from 2011 to 2016 at a large academic medical institution and two affiliated community sites. pCR was defined as ypT0/is ypN0. Fisher’s exact test and logistic regression analysis were used for statistical analysis.

Results

In this study (N = 121), pCR was numerically higher with pertuzumab-based regimens, including ddAC-THP (60%), TCHP (63%), THP (55%), as compared with ddAC-TH (46%). THP resulted in significantly less cycle delays due to toxicity compared to the other regimens (p = 0.02). THP also resulted in the least dose reductions, lowest rate of hospitalization, and lowest rate of treatment discontinuation.

Conclusions

Pertuzumab-based regimens, including THP, resulted in higher pCR rates as compared to ddAC-TH, with the THP regimen associated with the best tolerability among patients with localized HER2+ breast cancer. Given the various neoadjuvant regimens, additional studies are needed to determine optimal treatment sequencing and escalation/de-escalation strategies to personalize neoadjuvant regimens for localized HER2+ breast cancer.

Keywords

Neoadjuvant HER2 Pathologic complete response Pertuzumab Trastuzumab 

Notes

Funding

This work was supported by NIH Grant KL2 TR001100 (to L.S) and Susan G Komen CCR15224703 (to A.B.).

Compliance with Ethical Standards

Conflict of interest

All the authors declared that they have no relevant conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

10549_2018_4959_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (DOCX 12 KB)

References

  1. 1.
    Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182.  https://doi.org/10.1126/science.3798106 CrossRefGoogle Scholar
  2. 2.
    Elster N, Collins DM, Toomey S et al (2015) HER2-family signalling mechanisms, clinical implications and targeting in breast cancer. Breast Cancer Res Treat 149:5–15.  https://doi.org/10.1007/s10549-014-3250-x CrossRefPubMedGoogle Scholar
  3. 3.
    Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for Metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792.  https://doi.org/10.1056/NEJM200103153441101 CrossRefGoogle Scholar
  4. 4.
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672.  https://doi.org/10.1056/NEJMoa052306 CrossRefPubMedGoogle Scholar
  5. 5.
    Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684.  https://doi.org/10.1056/NEJMoa052122 CrossRefPubMedGoogle Scholar
  6. 6.
    Slamon D, Eiermann W, Robert N et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283.  https://doi.org/10.1056/NEJMoa0910383 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Joensuu H, Kellokumpu-Lehtinen P-L, Bono P et al (2006) Adjuvant Docetaxel or Vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 354:809–820.  https://doi.org/10.1056/NEJMoa053028 CrossRefPubMedGoogle Scholar
  8. 8.
    Mauri D, Pavlidis N, Ioannidis JPA (2005) Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst 97:188–194.  https://doi.org/10.1093/jnci/dji021 CrossRefPubMedGoogle Scholar
  9. 9.
    Rastogi P, Anderson SJ, Bear HD et al (2008) Preoperative chemotherapy: updates of national surgical adjuvant breast and bowel project protocols B-18 and B-27. J Clin Oncol 26:778–785.  https://doi.org/10.1200/JCO.2007.15.0235 CrossRefPubMedGoogle Scholar
  10. 10.
    King TA, Morrow M (2015) Surgical issues in patients with breast cancer receiving neoadjuvant chemotherapy. Nat Rev Clin Oncol 12:335–343.  https://doi.org/10.1038/nrclinonc.2015.63 CrossRefPubMedGoogle Scholar
  11. 11.
    Bardia A, Baselga J (2013) Neoadjuvant therapy as a platform for drug development and approval in breast cancer. Clin Cancer Res 19:6360–6370.  https://doi.org/10.1158/1078-0432.CCR-13-0916 CrossRefPubMedGoogle Scholar
  12. 12.
    Broglio KR, Quintana M, Foster M et al (2016) Association of pathologic complete response to neoadjuvant therapy in HER2-positive breast cancer with long-term outcomes: a meta-analysis. JAMA Oncol 2:751–760.  https://doi.org/10.1001/jamaoncol.2015.6113 CrossRefPubMedGoogle Scholar
  13. 13.
    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.  https://doi.org/10.1016/S0140-6736(13)62422-8 CrossRefPubMedGoogle Scholar
  14. 14.
    US Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER) Guidance for Industry: Pathological Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer: Use as an Endpoint to Support Accelerated Approval. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm305501.pdf. Accessed 13 Jul 2016
  15. 15.
    Gianni L, Pienkowski T, Im Y-H 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 13:25–32.  https://doi.org/10.1016/S1470-2045(11)70336-9 CrossRefPubMedGoogle Scholar
  16. 16.
    Schneeweiss A, Chia S, Hickish T 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.  https://doi.org/10.1093/annonc/mdt182 CrossRefPubMedGoogle Scholar
  17. 17.
    von Minckwitz G, Procter M, de Azambuja E et al (2017) Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med 377:122–131.  https://doi.org/10.1056/NEJMoa1703643 CrossRefGoogle Scholar
  18. 18.
    Wolff AC, Hammond MEH, Hicks DG 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 31:3997–4013.  https://doi.org/10.1200/JCO.2013.50.9984 CrossRefGoogle Scholar
  19. 19.
    Hammond MEH, Hayes DF, Dowsett M et al (2010) American society of clinical oncology/college of American pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28:2784–2795.  https://doi.org/10.1200/JCO.2009.25.6529 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Smith LA, Cornelius VR, Plummer CJ et al (2010) Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer 10:337.  https://doi.org/10.1186/1471-2407-10-337 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    van Dalen EC, Michiels EM, Caron HN, Kremer LC (2010) Different anthracycline derivates for reducing cardiotoxicity in cancer patients. Cochrane Database Syst Rev doi.  https://doi.org/10.1002/14651858.CD005006.pub4 CrossRefGoogle Scholar
  22. 22.
    Swain SM, Ewer MS, Viale G et al (2018) Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol 29:646–653.  https://doi.org/10.1093/annonc/mdx773 CrossRefPubMedGoogle Scholar
  23. 23.
    Citron ML, Berry DA, Cirrincione C et al (2003) randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of intergroup trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 21:1431–1439.  https://doi.org/10.1200/JCO.2003.09.081 CrossRefPubMedGoogle Scholar
  24. 24.
    Singh JC, Mamtani A, Barrio A et al (2017) pathologic complete response with neoadjuvant doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab and pertuzumab in patients with HER2-positive early stage breast cancer: a single center experience. Oncologist 22:139–143.  https://doi.org/10.1634/theoncologist.2016-0268 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Chan A, Delaloge S, Holmes FA et al (2016) Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 17:367–377.  https://doi.org/10.1016/S1470-2045(15)00551-3 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Laura Spring
    • 1
  • Andrzej Niemierko
    • 1
  • Stephanie Haddad
    • 1
  • Megan Yuen
    • 1
  • Amy Comander
    • 1
  • Kerry Reynolds
    • 1
  • Jennifer Shin
    • 1
  • Atul Bahn
    • 1
  • Elena Brachtel
    • 1
  • Michelle Specht
    • 1
  • Barbara L. Smith
    • 1
  • Alphonse Taghian
    • 1
  • Rachel Jimenez
    • 1
  • Jeffrey Peppercorn
    • 1
  • Steven J. Isakoff
    • 1
  • Beverly Moy
    • 1
  • Aditya Bardia
    • 1
  1. 1.Massachusetts General Hospital Cancer CenterHarvard Medical SchoolBostonUSA

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