Faculty, Staff and Student Publications

Publication Date

5-1-2025

Journal

Advances in Therapy

DOI

10.1007/s12325-024-03080-9

PMID

40048102

PMCID

PMC12006272

PubMedCentral® Posted Date

3-6-2025

PubMedCentral® Full Text Version

Post-print

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

Female, Humans, Antineoplastic Agents, Immunological, Camptothecin, Immunoconjugates, Immunohistochemistry, Neoplasms, Receptor, ErbB-2, Trastuzumab, Treatment Outcome, Clinical Trials, Phase II as Topic, Secondary Data Analysis, Advanced/metastatic solid tumors, Trastuzumab deruxtecan, HER2-expressing, HER2 testing

Published Open-Access

yes

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