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Subcutaneous Trastuzumab: A Review in HER2-Positive Breast Cancer

  • Young-A HeoEmail author
  • Yahiya Y. Syed
Adis Drug Evaluation
  • 20 Downloads

Abstract

A subcutaneous (SC) formulation of trastuzumab, a potent humanized anti-Human Epidermal growth factor Receptor 2 (HER2) receptor monoclonal antibody, with a recombinant hyaluronidase (Herceptin Hylecta™; Herceptin®) is indicated in the USA and EU for the treatment of HER2-positive breast cancer. In the phase III pivotal HannaH trial, SC trastuzumab was noninferior to the standard intravenous (IV) formulation of trastuzumab with respect to trough drug concentrations and pathological complete response in patients with HER2-positive early breast cancer. Other clinical outcomes, including event-free survival and overall survival rates, were generally similar between the formulation groups. SC trastuzumab had a manageable tolerability profile in patients with HER2-positive early or metastatic breast cancer, with the safety profile being generally similar to that of the IV formulation. In the phase III PrefHER and MetaspHER trials, more patients preferred SC over IV trastuzumab and more healthcare professionals expressed satisfaction with the SC formulation. Relative to IV trastuzumab, SC trastuzumab offers a quicker and more convenient dosage regimen, thereby potentially improving patient convenience, providing economic benefit and optimizing the use of medical resources. Thus, given the high preference for SC trastuzumab and its generally similar efficacy and tolerability profile to that of the IV formulation, SC trastuzumab is the preferred treatment of choice in patients receiving trastuzumab for the treatment of HER2-positive early or metastatic breast cancer.

Notes

Acknowledgements

During the peer review process, the manufacturer of SC trastuzumab was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with Ethical Standards

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Young-A Heo and Yahiya Syed are salaried employees of Adis International Ltd/Springer Nature, are responsible for the article content and declare no relevant conflicts of interest.

Supplementary material

11523_2019_684_MOESM1_ESM.docx (21 kb)
Supplementary material 1 (DOCX 21 kb)

References

  1. 1.
    Senkus E, Kyriakides S, Ohno S, et al. Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;26(Suppl 5):v8–30.CrossRefGoogle Scholar
  2. 2.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34.CrossRefGoogle Scholar
  3. 3.
    Dent S, Ammendolea C, Christofides A, et al. A multidisciplinary perspective on the subcutaneous administration of trastuzumab in HER2-positive breast cancer. Curr Oncol. 2019;26(1):e70–80.CrossRefGoogle Scholar
  4. 4.
    Mazzotta M, Krasniqi E, Barchiesi G, et al. Long-term safety and real-world effectiveness of trastuzumab in breast cancer. J Clin Med. 2019.  https://doi.org/10.3390/jcm8020254.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Cardoso F, Senkus E, Costa A, et al. 4th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 4). Ann Oncol. 2018;29(8):1634–57.CrossRefGoogle Scholar
  6. 6.
    National Comprehensive Cancer Network. NCCN guidelines: breast cancer. 2019. http://nccn.org. Accessed 15 Oct 2019.
  7. 7.
    Genentech Inc. Herceptin™ (trastuzumab injection, powder, lyophilized, for solution): US Prescribing Information. 2019. http://www.fda.gov/. Accessed 15 Oct 2019.
  8. 8.
    European Medicines Agency. Herceptin 150 mg powder for infusion and 600 mg solution for injection in vial: summary of product characteristics. 2019. http://www.ema.europa.eu/. Accessed 15 Oct 2019.
  9. 9.
    Genentech Inc. Herceptin Hylecta™ (trastuzumab and hyaluronidase-oysk injection, for subcutaneous use): US Prescribing Information. 2019. https://www.fda.gov/. Accessed 15 Oct 2019.
  10. 10.
    Sanford M. Subcutaneous trastuzumab: a review of its use in HER2-positive breast cancer. Target Oncol. 2014;9(1):85–94.CrossRefGoogle Scholar
  11. 11.
    Ismael G, Hegg R, Muehlbauer S, et al. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012;13(9):869–78.CrossRefGoogle Scholar
  12. 12.
    Jackisch C, Hegg R, Stroyakovskiy D, et al. HannaH phase III randomised study: association of total pathological complete response with event-free survival in HER2-positive early breast cancer treated with neoadjuvant-adjuvant trastuzumab after 2 years of treatment-free follow-up. Eur J Cancer. 2016;62:62–75.CrossRefGoogle Scholar
  13. 13.
    Jackisch C, Stroyakovskiy D, Pivot X, et al. Subcutaneous vs intravenous trastuzumab for patients with ERBB2-positive early breast cancer: final analysis of the HannaH phase 3 randomized clinical trial. JAMA Oncol. 2019.  https://doi.org/10.1001/jamaoncol.2019.0339.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Cicin I, Oukkal M, Mahfouf H, et al. An open-label, multinational, phase IIIb study to evaluate patient and satisfaction, safety and efficacy of subcutaneous administration of trastuzumab in patients with HER2-positive early breast cancer (ML28851) in adjuvant/neo-adjuvant setting [abstract no. 363 (PB-158)]. Eur J Cancer. 2018;92(Suppl 3):S102–3.CrossRefGoogle Scholar
  15. 15.
    Pivot X, Verma S, Fallowfield L, et al. Efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab as part of adjuvant therapy for HER2-positive early breast cancer: final analysis of the randomised, two-cohort PrefHER study. Eur J Cancer. 2017;86:82–90.CrossRefGoogle Scholar
  16. 16.
    Ludtke-Heckenkamp K, Kummel S, Ruf-Dordelmann A, et al. Second interim analysis of HerSCin, a German non-interventional study of subcutaneous trastuzumab for HER2-positive early breast cancer in routine clinical practice [abstract no. 178P]. Ann Oncol. 2017;28(Suppl 5):53–4.Google Scholar
  17. 17.
    Gligorov J, Ataseven B, Verrill M, et al. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHER phase III study’s primary analysis of 2573 patients. Eur J Cancer. 2017;82:237–46.CrossRefGoogle Scholar
  18. 18.
    Kummel S, Tondini CA, Abraham J, et al. Subcutaneous trastuzumab (H SC) with intravenous pertuzumab (P IV) and docetaxel (D IV) in HER2-positive advanced breast cancer (BC): MetaPHER second interim analysis [abstract no. 323P]. Ann Oncol. 2018;29(Suppl 8):viii103.Google Scholar
  19. 19.
    Pivot X, Gligorov J, Mueller V, et al. Preference for subcutaneous or intravenous administration of trastuzumab in patients with HER2-positive early breast cancer (PrefHER): an open-label randomised study. Lancet Oncol. 2013;14(10):962–70.CrossRefGoogle Scholar
  20. 20.
    Pivot X, Spano JP, Espie M, et al. Patients’ preference of trastuzumab administration (subcutaneous versus intravenous) in HER2-positive metastatic breast cancer: results of the randomised MetaspHER study. Eur J Cancer. 2017;82:230–6.CrossRefGoogle Scholar
  21. 21.
    Jackisch C, Muller V, Dall P, et al. Subcutaneous trastuzumab for HER2-positive breast cancer—evidence and practical experience in 7 German centers. Geburtshilfe Frauenheilkd. 2015;75(6):566–73.CrossRefGoogle Scholar
  22. 22.
    Valachis A, Carlsson L, Sundqvist M, et al. Use of subcutaneous and intravenous trastuzumab: real-world experience from three hospitals in Sweden [abstract no. P6-17-24]. Cancer Res. 2019;79(4 Suppl).Google Scholar
  23. 23.
    Jacquin JPP, Uwer L, Savignoni A, et al. Safety profile of subcutaneous trastuzumab in patients with HER2-positive early breast cancer: the French HERMIONE non-interventional prospective study [abstract no. 220P]. Ann Oncol. 2018;29(Suppl 8):viii70-1.Google Scholar
  24. 24.
    Syrios J, Pappa E, Volakakis N, et al. Real-world data on health-related quality of life assessment in patients with breast cancer receiving subcutaneous trastuzumab. Breast Cancer. 2018;12:1–10.Google Scholar
  25. 25.
    European Medicines Agency. Herceptin: CHMP assessment report. 2013. http://www.ema.europa.eu/. Accessed 29 Aug 2019.
  26. 26.
    Pivot X, Gligorov J, Muller V, et al. Patients’ preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHER study. Ann Oncol. 2014;25(10):1979–87.CrossRefGoogle Scholar
  27. 27.
    De Cock E, Pivot X, Hauser N, et al. A time and motion study of subcutaneous versus intravenous trastuzumab in patients with HER2-positive early breast cancer. Cancer Med. 2016;5(3):389–97.CrossRefGoogle Scholar
  28. 28.
    Jackisch C, Kim SB, Semiglazov V, et al. Subcutaneous versus intravenous formulation of Trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study. Ann Oncol. 2015;26(2):320–5.CrossRefGoogle Scholar
  29. 29.
    Jung KH, Ataseven B, Verrill M, et al. Adjuvant subcutaneous trastuzumab for HER2-positive early breast cancer: subgroup analyses of safety and active medical conditions by body weight in the SafeHer phase III study. Oncologist. 2018;23(10):1137–43.CrossRefGoogle Scholar
  30. 30.
    Food and Drug Administration. Clinical trial endpoints for the approval of cancer drugs and biologics. 2018. http://www.fda.gov/. Accessed 23 Jul 2019.
  31. 31.
    European Medicines Agency. Draft guideline on the role of the pathological complete response as an endpoint in neoadjuvant breast cancer studies. 2014. http://www.ema.europa.eu/. Accessed 23 Jul 2019.
  32. 32.
    Ponzetti C, Canciani M, Farina M, et al. Administrative risk quantification of subcutaneous and intravenous therapies in Italian centers utilizing the failure mode and effects analysis approach. Clinicoecon Outcomes Res. 2016;8:353–9.CrossRefGoogle Scholar
  33. 33.
    Hedayati E, Fracheboud L, Srikant V, et al. Economic benefits of subcutaneous trastuzumab administration: a single institutional study from Karolinska university hospital in Sweden. PLoS One. 2019.  https://doi.org/10.1371/journal.pone.0211783.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Farolfi A, Silimbani P, Gallegati D, et al. Resource utilization and cost saving analysis of subcutaneous versus intravenous trastuzumab in early breast cancer patients. Oncotarget. 2017;8(46):81343–9.CrossRefGoogle Scholar
  35. 35.
    Marty CB, Blein C, Borg MC, et al. A multi-center evaluation of clinical pathways cost and time using reallife data in 411 breast cancer patients treated with intravenous versus subcutaneous trastuzumab [abstract no. 373 (PB-168)]. Eur J Cancer. 2018;92(Suppl 3):S106–7.CrossRefGoogle Scholar
  36. 36.
    Todorovic V, Durutovic I, Ivanovska A, et al. Subcutaneous vs intravenous administration of trastuzumab in HER2 + breast cancer patients: a Montenegrin cost-minimization analysis [abstract no. PCN172]. Value Health. 2017;20(9):A443.CrossRefGoogle Scholar
  37. 37.
    Lopez-Vivanco G, Salvador J, Diez R, et al. Cost minimization analysis of treatment with intravenous or subcutaneous trastuzumab in patients with HER2-positive breast cancer in Spain. Clin Transl Oncol. 2017;19(12):1454–61.CrossRefGoogle Scholar
  38. 38.
    Lee VW, Cheng F. Cost-minimization analysis of trastuzumab intravenous versus trastuzumab subcutaneous regimen for breast cancer management in Hong Kong [abstract no. PCN57]. Value Health. 2018;21(Suppl 2):S16.CrossRefGoogle Scholar
  39. 39.
    O’Brien GL, O’Mahony C, Cooke K, et al. Cost minimization analysis of intravenous or subcutaneous trastuzumab treatment in patients with HER2-positive breast cancer in Ireland. Clin Breast Cancer. 2019;19(3):e440–51.CrossRefGoogle Scholar
  40. 40.
    Mylonas C, Skroumpelos A, Fountzilas G, et al. Cost minimization analysis of herceptin subcutaneous versus herceptin intravenous treatment for patients with HER2 + breast cancer in Greece. J Cancer Policy. 2017;13:11–7.CrossRefGoogle Scholar
  41. 41.
    Nixon NA, Hannouf MB, Verma S. The evolution of biosimilars in oncology, with a focus on trastuzumab. Curr Oncol. 2018;25(Suppl 1):S171–9.CrossRefGoogle Scholar
  42. 42.
    Quartino AL, Hillenbach C, Li J, et al. Population pharmacokinetic and exposure-response analysis for trastuzumab administered using a subcutaneous “manual syringe” injection or intravenously in women with HER2-positive early breast cancer. Cancer Chemother Pharmacol. 2016;77(1):77–88.CrossRefGoogle Scholar
  43. 43.
    Wynne CJ, Ellis-Pegler RB, Waaka DS, et al. Comparative pharmacokinetics of subcutaneous trastuzumab administered via handheld syringe or proprietary single-use injection device in healthy males. Cancer Chemother Pharmacol. 2013;72(5):1079–87.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Springer NatureAucklandNew Zealand

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