Trastuzumab deruxtecan and other HER2-targeting agents for the treatment of HER2-positive gastric cancer

Expert Rev Anticancer Ther. 2021 Nov;21(11):1193-1201. doi: 10.1080/14737140.2021.1982698. Epub 2021 Sep 29.

Abstract

Introduction: Although various new drugs have been developed, the prognosis of therapeutic advances for metastatic gastric cancer is insufficient. Trastuzumab deruxtecan (T-DXd), a new human epidermal growth factor receptor 2 (HER2)-targeting antibody-drug conjugate (ADC), has demonstrated promising results in clinical trials.

Areas covered: In this article, we review the history of anti-HER2 ADCs and focus on the efficacy and safety of T-DXd and describe the development of new anti-HER2 drugs.

Expert opinion: So far, no other anti-HER2 ADCs have demonstrated efficacy in patients with HER2-positive advanced gastric cancer with two or more previous lines of chemotherapy, including trastuzumab. However, a new drug, T-DXd, has shown a significantly higher objective response rate and a longer overall survival and, thus, was approved in Japan. In the future, new anti-HER2 drugs and/or treatment strategies including T-DXd along with cytotoxic chemotherapy or immune checkpoint inhibitors will be developed.

Keywords: Antibody–drug conjugate; HER2; T-DXD; gastric cancer; trastuzumab deruxtecan.

Publication types

  • Review

MeSH terms

  • Camptothecin / analogs & derivatives
  • Humans
  • Immunoconjugates* / adverse effects
  • Receptor, ErbB-2 / metabolism
  • Stomach Neoplasms* / drug therapy
  • Trastuzumab

Substances

  • Immunoconjugates
  • trastuzumab deruxtecan
  • Receptor, ErbB-2
  • Trastuzumab
  • Camptothecin