Neratinib in extended adjuvant therapy for HER2-positive early breast cancer
Abstract
HER2 overexpression is found in approximately 20% of patients with breast cancer and is associated with an unfavorable prognosis. The use of chemotherapy and targeted therapies blocking HER2 function in patients with early HER2 positive breast cancer has led to significant clinical benefits. Despite this, approximately 25% of patients initially treated with trastuzumab experience recurrence of invasive disease within 5 years of completion of adjuvant treatment. Neratinib is an oral, irreversible, small molecule tyrosine kinase inhibitor blocking the intracellular domain of the HER1, HER2 and HER4 receptor, whose activity in extended anti-HER2 adjuvant treatment in HER2-positive early breast cancer patients has been confirmed in ExteNET trial. It has been shown that the use of extended therapy with neratinib after adjuvant trastuzumab treatment in patients with early HER2-positive breast cancer led to a 33% reduction in the risk of invasive disease recurring, with a greater effect observed in ER/PgR positive patients and those with involvement 4 and more lymph nodes.
Keywords: neratinibextended adjuvant treatmentHER2-positive early breast cancer
References
- Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785): 177–182.
- Lambertini M, Pondé NF, Solinas C, et al. Adjuvant trastuzumab: a 10-year overview of its benefit. Expert Rev Anticancer Ther. 2017; 17(1): 61–74.
- Cameron D, Piccart-Gebhart MJ, Gelber RD, et al. Herceptin Adjuvant (HERA) Trial Study Team. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017; 389(10075): 1195–1205.
- Piccart-Gebhart M, Holmes E, Baselga J, et al. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III adjuvant lapatinib and/or trastuzumab treatment optimization trial. J Clin Oncol. 2016; 34(10): 1034–1042.
- Slamon DL, Swain SM, Buyse M, et al. Primary results from BETH, a phase 3 controlled study of adjuvant chemotherapy and trastuzumab ± bevacizumab in patients with HER2¬positive, node¬positive, or high¬risk node¬negative breast cancer. Cancer Res 2013; 73 (suppl 24): S1–03 (abstr).
- von Minckwitz G, Procter M, de Azambuja E, et al. APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017; 377(2): 122–131.
- Burstein HJ, Sun Y, Dirix LY, et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J Clin Oncol. 2010; 28(8): 1301–1307.
- Wong KK, Fracasso PM, Bukowski RM, et al. A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors. Clin Cancer Res. 2009; 15(7): 2552–2558.
- Wissner A, Mansour TS. The development of HKI-272 and related compounds for the treatment of cancer. Arch Pharm (Weinheim). 2008; 341(8): 465–477.
- Rabindran SK, Discafani CM, Rosfjord EC, et al. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res. 2004; 64(11): 3958–3965.
- Zhang Y, Zhang J, Liu C, et al. Neratinib induces ErbB2 ubiquitylation and endocytic degradation via HSP90 dissociation in breast cancer cells. Cancer Lett. 2016; 382(2): 176–185.
- Martin M, Bonneterre J, Geyer CE, et al. A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer. Eur J Cancer. 2013; 49(18): 3763–3772.
- Chan A, Delaloge S, Holmes F, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology. 2016; 17(3): 367–377.
- Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014; 32(33): 3744–3752.
- Perez EA, Suman VJ, Davidson NE, et al. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011; 29(34): 4491–4497.
- Slamon D, Eiermann W, Robert N, et al. BCIRG 006 Phase III trial comparing AC→T with AC→TH and with TCH in the adjuvant treatment of HER2-amplified early breast cancer patients: third planned efficacy analysis. 2009.
- Dhillon S, Dhillon S, Dhillon S. Neratinib in Early-Stage Breast Cancer: A Profile of Its Use in the EU. Clin Drug Investig. 2019; 39(2): 221–229.
- Gnant M, Martin M, Holmes FA, et al. Efficacy of neratinib in hormone receptor-positive patients who initiated treatment within 1 year of completing trastuzumab-based adjuvant therapy in HER2+ early stage breast cancer: subgroup analyses from the phase III ExteNET trial. Presented at the 41st San Antonio Breast Cancer Symposium, Dec 4-8, 2018, San Antonio, Tx, USA.
- Martin M, Holmes FA, Ejlertsen B, et al. ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017; 18(12): 1688–1700.
- Giuliano M, Trivedi MV, Schiff R. Bidirectional Crosstalk between the Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 Signaling Pathways in Breast Cancer: Molecular Basis and Clinical Implications. Breast Care (Basel). 2013; 8(4): 256–262.
- Cardoso F, Kyriakides S, Ohno S, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2019; 30(8): 1194–1220.
- www.nice.org.uk/guidance/ta612.