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.

Cancer Research Institute Seoul National University College of Medicine Seoul Republic of Korea

Department of Investigational Cancer Therapeutics The University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Department of Medical Oncology Hospital Universitario 12 de Octubre Madrid Spain

Department of Medicine Weill Cornell Medical College New York NY USA

Department of Obstetrics and Gynecology Yonsei Cancer Center and Severance Hospital Yonsei University College of Medicine Seoul Republic of Korea

Department of Oncology and Hemato Oncology Università degli Studi di Milano Milan Italy

Department of Oncology Asan Medical Center University of Ulsan College of Medicine Seoul Republic of Korea

Department of Oncology Palacký University Medical School and University Hospital Olomouc Czechia

Early Phase Clinical Trials Unit Maria Skłodowska Curie National Research Institute of Oncology Warsaw Poland

Experimental Therapeutics in Cancer Department of Medical Oncology Hospital Clínico San Carlos Madrid Spain

Gynaecology Unit The Royal Marsden NHS Foundation Trust London UK

Gynecologic Medical Oncology Service Memorial Sloan Kettering Cancer Center New York NY USA

Healthcare Department Moscow City Oncology Hospital No 62 Moscow Russian Federation

Institute of Cancer Research London UK

Integrated Major in Innovative Medical Science Seoul National University Graduate School Seoul Republic of Korea

Medical Oncology Department and Programme in Solid Tumours CIMA Cancer Center Clínica Universidad de Navarra Madrid Spain

Medical Oncology Service Vall d'Hebron Barcelona Hospital Campus Barcelona Spain

Niguarda Cancer Center Grande Ospedale Metropolitano Niguarda Milan Italy

Oncology Biometrics Oncology R and D AstraZeneca Cambridge UK

Oncology R and D AstraZeneca Gaithersburg MD USA

Seoul National University Hospital Seoul Republic of Korea

Zobrazit více v PubMed

Oaknin A, Lee J-Y, Makker V, et al. Efficacy of trastuzumab deruxtecan in HER2-expressing solid tumors by enrollment HER2 IHC status: post hoc analysis of DESTINY-PanTumor02. Adv Ther. 2024;41:4125–39. 10.1007/s12325-024-02975-x. PubMed PMC