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

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.

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Publication Details

Journal
Advances in Therapy
Published
2025-03-06
DOI
https://doi.org/10.1007/s12325-024-03080-9
Citations
4
Primary Topic
HER2/EGFR in Cancer Research
Type
article
Field-Weighted Citation Impact
4.18

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article

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

Soham D. Puvvada, Aránzazu Manzano, Antonio González-Martı́n, Bohuslav Melichar et al.
4 citations
Advances in Therapy
HER2/EGFR in Cancer Research
4.18
article

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

Soham D. Puvvada, Aránzazu Manzano, Antonio González-Martı́n, Bohuslav Melichar, Salvatore Siena, Iwona Ługowska, Kyung Hae Jung, Do‐Youn Oh, Anitra Fielding, Susana Banerjee, Ana Oaknin, Daniil Stroyakovskiy, Jung‐Yun Lee, Vicky Makker, Funda Meric‐Bernstam, Luís Manso, Ann Smith
article en
4 citations

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.

Advances in TherapyVol. 42(5)
AstraZeneca (United Kingdom) (GB), Ulsan College (KR), Royal Marsden NHS Foundation Trust (GB), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), Seoul National University (KR), Institute of Cancer Research (GB), University of Milan (IT), Yonsei University (KR), Cornell University (US), Severance Hospital (KR), Asan Medical Center (KR), Seoul National University Hospital (KR), Hospital Clínico San Carlos (ES), University of Ulsan (KR), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), Hospital Universitario 12 De Octubre (ES), University Hospital Olomouc (CZ), Vall d'Hebron Hospital Universitari (ES), Clinica Universidad de Navarra (ES), AstraZeneca (United States) (US), The Maria Sklodowska-Curie National Research Institute of Oncology (PL), Moscow City Oncology Hospital №62 (RU), Palacký University Olomouc (CZ)
AstraZeneca
Zero hunger
Openalex Percentile: Top 6%
HER2/EGFR in Cancer Research
4.18
DOIOpen Access PDFOpenAlex
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