INTRODUCTION: DESTINY-PanTumor02 (NCT04482309) evaluated the efficacy and safety of trastuzumab deruxtecan (T-DXd) in pretreated patients with human epidermal growth factor receptor 2 (HER2)-expressing [immunohistochemistry (IHC) 3+/2+] solid tumors across seven cohorts: endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, and other. Subgroup analyses by HER2 status were previously reported by central HER2 IHC testing, determined at enrollment or confirmed retrospectively. Reflecting the testing methods available in clinical practice, most patients (n = 202; 75.7%) were enrolled based on local HER2 IHC testing. Here, we report outcomes by HER2 IHC status as determined by the local or central test results used for study enrollment. METHODS: This phase 2, open-label study evaluated T-DXd (5.4 mg/kg once every 3 weeks) for HER2-expressing (IHC 3+/2+ by local or central testing) locally advanced or metastatic disease after ≥ 1 systemic treatment or without alternative treatments. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival. RESULTS: In total, 111 (41.6%) and 151 (56.6%) patients were enrolled with IHC 3+ and IHC 2+ tumors, respectively. In patients with IHC 3+ tumors, investigator-assessed confirmed ORR was 51.4% [95% confidence interval (CI) 41.7, 61.0], and median DOR was 14.2 months (95% CI 10.3, 23.6). In patients with IHC 2+ tumors, investigator-assessed ORR was 26.5% (95% CI 19.6, 34.3), and median DOR was 9.8 months (95% CI 4.5, 12.6). Safety was consistent with the known profile of T-DXd. CONCLUSION: In line with previously reported results, T-DXd demonstrated clinically meaningful benefit in patients with HER2-expressing tumors, with the greatest benefit in patients with IHC 3+ tumors. These data support the antitumor activity of T-DXd in HER2-expressing solid tumors, irrespective of whether patients are identified by local or central HER2 IHC testing.

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 Czech Republic

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 Russia

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 Institute of Oncology 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

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