Download PDF
Open Access
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2019; 40(04): 556-558
DOI: 10.4103/ijmpo.ijmpo_264_19
Drug Review

Trastuzumab Deruxtecan: A Quantum Leap in HER2‑Positive Breast Cancer

Authors

  • Manikandan Dhanushkodi

    Department of Medical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India

Financial support and sponsorship Nil.
Further Information
Also available at
  Permissions and Reprints
Preview

Abstract

Docetaxel, trastuzumab, and pertuzumab, known as THP, is the preferred first-line treatment for HER2-positive advanced breast cancer, and the second-line drug of choice is trastuzumab emtansine. Most patients eventually develop resistance to systemic therapy. Trastuzumab deruxtecan, a novel HER2-targeted antibody drug conjugate, has shown to be promising in this subset. It is a HER2-targeted antibody drug conjugate structurally composed of humanized anti-HER2 monoclonal antibody, cleavable tetra-peptide-based liker, and a potent payload (topoisomerase 1 inhibitor: Exatecan). A phase 2 trial of heavily pretreated advanced HER2-positive breast cancer (median of six lines of prior therapy) showed an overall response of 61% and a median progression-free survival of 16 months. In December 2019, the Food and Drug Administration announced accelerated approval of trastuzumab deruxtecan for HER2-positive advanced breast cancer patients who were prior exposed to two or more lines of anti-HER2 therapy in a metastatic setting.

Keywords

Advanced breast cancer - HER2 positive - trastuzumab deruxtecan


Publication History

Received: 23 December 2019

Accepted: 03 January 2020

Article published online:
03 June 2021

© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M. et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 2015; 372: 724-34
    CrossrefPubMedSearch in Google Scholar
  • 2 Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J. et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012; 367: 1783-91
    CrossrefPubMedSearch in Google Scholar
  • 3 Pohlmann PR, Mayer IA, Mernaugh R. Resistance to trastuzumab in breast cancer. Clin Cancer Res 2009; 15: 7479-91
    CrossrefPubMedSearch in Google Scholar
  • 4 Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA. et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med 2019
  • 5 Xu Z, Guo D, Jiang Z, Tong R, Jiang P, Bai L. et al. Novel HER2-targeting antibody-drug conjugates of trastuzumab beyond T-DM1 in breast cancer: Trastuzumab deruxtecan (DS-8201a) and (Vic-) trastuzumab duocarmazine (SYD985). Eur J Med Chem 2019; 183: 111682
    CrossrefPubMedSearch in Google Scholar
  • 6 Iwata TN, Ishii C, Ishida S, Ogitani Y, Wada T, Agatsuma T. A HER2-targeting antibody-drug conjugate, trastuzumab deruxtecan (DS-8201a), enhances antitumor immunity in a mouse model. Mol Cancer Ther 2018; 17: 1494-503
    CrossrefPubMedSearch in Google Scholar
  • 7 Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C. et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: A dose-expansion, phase 1 study. Lancet Oncol 2019; 20: 816-26
    CrossrefPubMedSearch in Google Scholar
  • 8 Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K. et al. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: A phase 1 dose-escalation study. Lancet Oncol 2017; 18: 1512-22
    CrossrefPubMedSearch in Google Scholar
  • 9 Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K. et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med 2019
  • 10 Nakada T, Sugihara K, Jikoh T, Abe Y, Agatsuma T. The latest research and development into the antibody-drug conjugate, [fam-] trastuzumab deruxtecan (DS-8201a), for HER2 cancer therapy. Chem Pharm Bull (Tokyo) 2019; 67: 173-85
    CrossrefPubMedSearch in Google Scholar
  • 11 Modi S, Tsurutani J, Tamura K, Park H, Sagara Y, Murthy R. et al. Abstract P6-17-02: Trastuzumab deruxtecan (DS-8201a) in subjects with HER2-low expressing breast cancer: Updated results of a large phase 1 study. Cancer Res 2019; 79: P6-17-02
    Search in Google Scholar
  • 12 Saura C, Oliveira M, Feng YH, Dai MS, Hurvitz SA, Kim SB. Neratinib + capecitabine versus lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with ≥2 HER2-directed regimens: Findings from the multinational, randomized, phase III NALA trial. J Clin Oncol 2019; 37: 1002
    CrossrefSearch in Google Scholar
  • 13 Rugo HS, Im SA, Wright GL, Escriva-de-Romani S, DeLaurentiis M, Cortes J. SOPHIA primary analysis: A phase 3 (P3) study of margetuximab (M)+chemotherapy ũ versus trastuzumab (T)+C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx). J Clin Oncol 2019;37