RSS-Feed abonnieren

DOI: 10.4103/ijmpo.ijmpo_264_19
Trastuzumab Deruxtecan: A Quantum Leap in HER2‑Positive Breast Cancer
Financial support and sponsorship Nil.
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.
Publikationsverlauf
Eingereicht: 23. Dezember 2019
Angenommen: 03. Januar 2020
Artikel online veröffentlicht:
03. Juni 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
- 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
- 3 Pohlmann PR, Mayer IA, Mernaugh R. Resistance to trastuzumab in breast cancer. Clin Cancer Res 2009; 15: 7479-91
-
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
- 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
- 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
- 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
-
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
- 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
- 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
-
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