The Potential of Trastuzumab Deruxtecan as a Tissue Agnostic Drug

Oncology. 2023;101(12):836-842. doi: 10.1159/000533866. Epub 2023 Aug 31.

Abstract

Background: Many modern anticancer drugs are designed to target specific molecular alterations harbored by the cancer. If a specific drug is able to target these alterations, regardless of the organ or tissue in which the cancer originates, it will often be characterized as a tissue- or tumor agnostic drug. According to the Food and Drug Administration (FDA), a tissue-agnostic drug refers to a drug that targets a specific molecular alteration across multiple cancer types, as defined by organ, tissue, or tumor type.

Summary: Over the last 6 years, the FDA has approved seven tissue-agnostic drugs, and more are anticipated in the future. One promising candidate for a tissue-agnostic classification is the antibody-drug conjugate trastuzumab deruxtecan (T-DXd). Currently, T-DXd is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive and HER2-low breast cancer, HER2-positive gastric or gastroesophageal junction adenocarcinoma, and non-small cell lung cancer with activating HER2 mutations. Ongoing clinical research is exploring the potential of T-DXd in various solid tumors that harbor specific HER2 molecular alterations, and encouraging results, including the interim data from the DESTINY-PanTumor02 trial, have been published, which suggest a tissue-agnostic potential.

Key messages: Published phase I data as well as the interim results from the phase II DESTINY-PanTumor02 trial indicates that patients with different HER2-positive advanced solid tumors may benefit from treatment with T-DXd. Based on the currently available data, it seems likely that T-DXd possesses pantumor activity. However, different clinical trials are ongoing, and it will be necessary to see the results from these trials before drawing a final conclusion. When discussing tissue-agnostic potential, it is important to add that for most of the patients enrolled in the DESTINY-PanTumor02 and other trials, few treatment alternatives seem to exist, and T-DXd might be able to cover an unmet medical need.

Keywords: Companion diagnostics; DESTINY-PanTumor02; Human epidermal growth factor receptor 2; Tissue-agnostic drug; Trastuzumab deruxtecan.

Publication types

  • Review

MeSH terms

  • Breast Neoplasms*
  • Camptothecin
  • Carcinoma, Non-Small-Cell Lung*
  • Female
  • Humans
  • Immunoconjugates* / therapeutic use
  • Lung Neoplasms*
  • Receptor, ErbB-2
  • Trastuzumab / therapeutic use

Substances

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