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Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02
A. Oaknin, JY. Lee, V. Makker, DY. Oh, S. Banerjee, A. González-Martín, KH. Jung, I. Ługowska, L. Manso, A. Manzano, B. Melichar, S. Siena, D. Stroyakovskiy, A. Fielding, S. Puvvada, A. Smith, F. Meric-Bernstam
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, klinické zkoušky, fáze II, multicentrická studie
Grantová podpora
P30 CA008748
NCI NIH HHS - United States
- MeSH
- dospělí MeSH
- imunohistochemie * MeSH
- imunokonjugáty terapeutické užití MeSH
- kamptothecin analogy a deriváty terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- protinádorové látky imunologicky aktivní terapeutické užití MeSH
- receptor erbB-2 * metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- trastuzumab * terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
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 Medical Oncology Hospital Universitario 12 de Octubre Madrid Spain
Department of Medicine Weill Cornell Medical College New York NY USA
Department of Oncology and Hemato Oncology Università degli Studi di Milano Milan Italy
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
Niguarda Cancer Center Grande Ospedale Metropolitano Niguarda Milan Italy
Oncology Biometrics Oncology R and D AstraZeneca Cambridge UK
Citace poskytuje Crossref.org
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