دورية أكاديمية
أعرض في EDS

Phase II study (KAMELEON) of single-agent T-DM1 in patients with HER2-positive advanced urothelial bladder cancer or pancreatic cancer/cholangiocarcinoma.

التفاصيل البيبلوغرافية
العنوان: Phase II study (KAMELEON) of single-agent T-DM1 in patients with HER2-positive advanced urothelial bladder cancer or pancreatic cancer/cholangiocarcinoma.
المؤلفون: de Vries EGE; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Rüschoff J; Targos Molecular Pathology GmbH, Kassel, Germany., Lolkema M; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Tabernero J; Vall d'Hebron Hospital Campus and Institute of Oncology (VHIO), UVic-UCC, IOB-Quiron, Barcelona, Spain., Gianni L; Michelangelo Foundation, Milan, Italy., Voest E; Netherlands Cancer Institute, Amsterdam, The Netherlands.; Oncode Institute, Amsterdam, The Netherlands., de Groot DJA; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Castellano D; Medical Oncology Department, Hospital Universitario 12 de Octubre, i + 12 Research Institute, Madrid, Spain., Erb G; F. Hoffmann-La Roche Ltd., Basel, Switzerland., Naab J; F. Hoffmann-La Roche Ltd., Basel, Switzerland., Donica M; F. Hoffmann-La Roche Ltd., Basel, Switzerland., Deurloo R; F. Hoffmann-La Roche Ltd., Basel, Switzerland., van der Heijden MS; Netherlands Cancer Institute, Amsterdam, The Netherlands., Viale G; IEO, European Institute of Oncology IRCCS, Milan, Italy.; University of Milan, Milan, Italy.
المصدر: Cancer medicine [Cancer Med] 2023 Jun; Vol. 12 (11), pp. 12071-12083. Date of Electronic Publication: 2023 Apr 29.
نوع المنشور: Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: John Wiley & Sons Ltd Country of Publication: United States NLM ID: 101595310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2045-7634 (Electronic) Linking ISSN: 20457634 NLM ISO Abbreviation: Cancer Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Malden, MA] : John Wiley & Sons Ltd., c2012-
مواضيع طبية MeSH: Maytansine* , Breast Neoplasms*/pathology , Cholangiocarcinoma* , Carcinoma, Transitional Cell* , Pancreatic Neoplasms*/drug therapy , Pancreatic Neoplasms*/genetics , Urinary Bladder Neoplasms*/drug therapy , Urinary Bladder Neoplasms*/genetics , Bile Duct Neoplasms*, Humans ; Female ; Trastuzumab ; Antibodies, Monoclonal, Humanized ; Ado-Trastuzumab Emtansine ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Bile Ducts, Intrahepatic/pathology ; Pancreatic Neoplasms
مستخلص: The antibody-drug conjugate trastuzumab emtansine (T-DM1) is approved for human epidermal growth factor receptor 2 (HER2/ERBB2)-positive breast cancer. We aimed to study tumor HER2 expression and its effects on T-DM1 responses in patients with HER2-positive urothelial bladder cancer (UBC) or pancreatic cancer (PC)/cholangiocarcinoma (CC). In the phase II KAMELEON study (NCT02999672), HER2 status was centrally assessed by immunohistochemistry, with positivity defined as non-focal homogeneous or heterogeneous overexpression of HER2 in ≥30% of stained cells. We also performed exploratory biomarker analyses (e.g., gene-protein assay) on tissue samples collected from study participants and consenting patients who failed screening. Of the 284 patients successfully screened for HER2 status (UBC, n = 69; PC/CC, n = 215), 13 with UBC, four with PC, and three with CC fulfilled eligibility criteria. Due to recruitment difficulty, the sponsor terminated KAMELEON prematurely. Of the five responders in the UBC cohort (overall response rate, 38.5%), HER2 expression was heterogeneous in two and homogeneous in three. The one responder in the PC/CC cohort had PC, and the tumor displayed homogeneous expression. In the biomarker-evaluable population, composed of screen-failed and enrolled patients, 24.3% (9/37), 1.5% (1/66), and 8.2% (4/49) of those with UBC, PC, or CC, respectively, had HER2-positive tumors. In a gene-protein assay combining in situ hybridization with immunohistochemistry, greater HER2 homogeneity was associated with increased ERBB2 amplification ratio. In conclusion, KAMELEON showed that some patients with HER2-positive UBC or PC can respond to T-DM1 and provided insight into the prevalence of HER2 positivity and expression patterns in three non-breast tumor types.
(© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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فهرسة مساهمة: Keywords: HER2-positive; KAMELEON; pancreatic cancer; trastuzumab emtansine; urothelial bladder cancer
المشرفين على المادة: P188ANX8CK (Trastuzumab)
14083FR882 (Maytansine)
0 (Antibodies, Monoclonal, Humanized)
SE2KH7T06F (Ado-Trastuzumab Emtansine)
EC 2.7.10.1 (Receptor, ErbB-2)
تواريخ الأحداث: Date Created: 20230429 Date Completed: 20230620 Latest Revision: 20231213
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10278525
DOI: 10.1002/cam4.5893
PMID: 37119523
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-7634
DOI:10.1002/cam4.5893