Summary of Research: Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02

Adv Ther. 2025 May;42(5):2015-2018. doi: 10.1007/s12325-024-03080-9. Epub 2025 Mar 6.

Abstract

of the original article, 'Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02'. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate, which is a chemotherapy with a linker (deruxtecan) joined to an antibody (trastuzumab). Trastuzumab binds to the human epidermal growth factor receptor 2 (HER2) protein on cancer cells, where it releases the chemotherapy to kill these cells. The DESTINY-PanTumor02 clinical study tested the effectiveness of T-DXd for people with various HER2-expressing cancers and the safety of treatment. Previous results from DESTINY-PanTumor02 showed that T-DXd had antitumor activity, and the greatest effects were seen in people with the highest tumor level of HER2 [defined as immunohistochemistry (IHC) 3+]. In this previous analysis, the HER2 expression was measured at a central laboratory. In clinical practice, HER2 expression will likely be measured at a local laboratory, so understanding whether T-DXd has similar effects regardless of how HER2 expression is measured is important. Here, we looked at the effects of T-DXd based on the HER2 test result used to determine a person's eligibility for the study, which could be measured using a local or central laboratory. In people with IHC 3+ tumors (where HER2 was measured at a local or central laboratory), 51% had a decrease in the size or number of tumors, according to established criteria (referred to as an objective response), while, in people with IHC 2+ tumors, 26% had an objective response. Side effects with T-DXd were consistent with previous studies. These results confirm T-DXd has antitumor effects in HER2-expressing cancers where the HER2 expression is measured by a local or central laboratory.

Keywords: Advanced/metastatic solid tumors; HER2 testing; HER2-expressing; Trastuzumab deruxtecan.

MeSH terms

  • Antineoplastic Agents, Immunological* / therapeutic use
  • Camptothecin* / administration & dosage
  • Camptothecin* / adverse effects
  • Camptothecin* / analogs & derivatives
  • Camptothecin* / therapeutic use
  • Clinical Trials, Phase II as Topic
  • Female
  • Humans
  • Immunoconjugates* / adverse effects
  • Immunoconjugates* / therapeutic use
  • Immunohistochemistry
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Receptor, ErbB-2* / metabolism
  • Secondary Data Analysis
  • Trastuzumab* / adverse effects
  • Trastuzumab* / therapeutic use
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Immunological
  • Camptothecin
  • ERBB2 protein, human
  • Immunoconjugates
  • Receptor, ErbB-2
  • Trastuzumab
  • trastuzumab deruxtecan