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Targeted Therapy in Salivary Gland Cancer: Prevalence of a Selected Panel of Actionable Molecular Alterations in a German Tertiary Referral Center Patient Cohort

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Title: Targeted Therapy in Salivary Gland Cancer: Prevalence of a Selected Panel of Actionable Molecular Alterations in a German Tertiary Referral Center Patient Cohort
Authors: Maximilian Linxweiler, Silke Wemmert, Felix Leon Braun, Sandrina Körner, Lukas Alexander Brust, Moritz Knebel, Gilbert Georg Klamminger, Mathias Wagner, Luc G. T. Morris, Jan Philipp Kühn
Source: Mol Diagn Ther
Publisher Information: Springer Science and Business Media LLC, 2024.
Publication Year: 2024
Subject Terms: Male, Adult, Aged, 80 and over, ddc:610, Female [MeSH], Aged, 80 and over [MeSH], Aged [MeSH], Adult [MeSH], Receptor, ErbB-2/metabolism [MeSH], Humans [MeSH], Tertiary Care Centers [MeSH], Salivary Gland Neoplasms/metabolism [MeSH], Receptors, Androgen/metabolism [MeSH], Receptor, ErbB-2/genetics [MeSH], Middle Aged [MeSH], Receptors, Androgen/genetics [MeSH], Germany/epidemiology [MeSH], Immunohistochemistry [MeSH], Molecular Targeted Therapy [MeSH], Male [MeSH], Salivary Gland Neoplasms/genetics [MeSH], Biomarkers, Tumor/genetics [MeSH], Original Research Article, Salivary Gland Neoplasms/drug therapy [MeSH], Salivary Gland Neoplasms/pathology [MeSH], Salivary Gland Neoplasms/epidemiology [MeSH], In Situ Hybridization, Fluorescence [MeSH], Middle Aged, Salivary Gland Neoplasms, Immunohistochemistry, Tertiary Care Centers, Germany, Biomarkers, Tumor, Humans, Female, Molecular Targeted Therapy, In Situ Hybridization, Fluorescence, Aged
Description: Salivary gland carcinomas (SGC) are a heterogeneous group of malignancies, with 24 subtypes defined by the World Health Organization (WHO). The standard of therapy is surgical resection, with adjuvant radiotherapy in most cases. However, disease recurrence (R) or metastasis (M) is common and no active systemic therapies are currently available for RM-SGC resulting in a 5-year survival rate of only 20%.Overall, 55 SGC patients with seven different histological tumor subtypes were included in this study. formalin-fixed paraffin-embedded (FFPE) tissue samples were used for immunohistochemical (IHC) staining targeting HER2/neu, androgen receptor (AR), PD-L1, EGFR, panTRK, and TROP2. Fluorescence in situ hybridization (FISH) was performed for detecting HER2/neu amplifications and NTRK1/2/3 translocations in selected cases with relevant HER2/neu and panTRK protein expression, respectively. IHC and FISH results were correlated with patients' clinical and histopathological data.The overall prevalence of druggable molecular alterations, defined as an immunoreactive score ≥ 9 in at least one of the analyzed targets, was 54.4% with the highest percentage in oncocytic carcinomas (100%) and lowest percentage in acinic cell carcinomas (10%). EGFR overexpression proved to be the most common alteration (32.7% of cases) followed by overexpression of TROP2 (27.3%), AR (10.9%), HER2/neu (7.3%), PD-L1 (1.8%), and panTRK (1.8%). HER2/neu amplifications were found in 50% and NTRK translocations were found in 100% of all cases with elevated Her2/neu and panTRK protein expression, respectively.Our data indicate that targeted therapy using e.g., trastuzumab deruxtecan, bicalutamide, pembrolizumab, cetuximab, entrectinib or sacituzumab govitecan might be a promising option especially for a relevant subset of patients with RM-SGC not suitable for salvage surgery. However, evidence from clinical studies regarding response rates to these therapies remains sparse, which underlines the need of multicenter clinical trials.
Document Type: Article
Other literature type
Language: English
ISSN: 1179-2000
1177-1062
DOI: 10.1007/s40291-024-00750-w
DOI: 10.22028/d291-44273
Access URL: https://pubmed.ncbi.nlm.nih.gov/39485665
https://repository.publisso.de/resource/frl:6498163
Rights: CC BY NC
URL: http://creativecommons.org/licenses/by-nc/4.0/Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (http://creativecommons.org/licenses/by-nc/4.0/) .
Accession Number: edsair.doi.dedup.....e17468210b577da9f6bf041de65e705b
Database: OpenAIRE
Description
Abstract:Salivary gland carcinomas (SGC) are a heterogeneous group of malignancies, with 24 subtypes defined by the World Health Organization (WHO). The standard of therapy is surgical resection, with adjuvant radiotherapy in most cases. However, disease recurrence (R) or metastasis (M) is common and no active systemic therapies are currently available for RM-SGC resulting in a 5-year survival rate of only 20%.Overall, 55 SGC patients with seven different histological tumor subtypes were included in this study. formalin-fixed paraffin-embedded (FFPE) tissue samples were used for immunohistochemical (IHC) staining targeting HER2/neu, androgen receptor (AR), PD-L1, EGFR, panTRK, and TROP2. Fluorescence in situ hybridization (FISH) was performed for detecting HER2/neu amplifications and NTRK1/2/3 translocations in selected cases with relevant HER2/neu and panTRK protein expression, respectively. IHC and FISH results were correlated with patients' clinical and histopathological data.The overall prevalence of druggable molecular alterations, defined as an immunoreactive score ≥ 9 in at least one of the analyzed targets, was 54.4% with the highest percentage in oncocytic carcinomas (100%) and lowest percentage in acinic cell carcinomas (10%). EGFR overexpression proved to be the most common alteration (32.7% of cases) followed by overexpression of TROP2 (27.3%), AR (10.9%), HER2/neu (7.3%), PD-L1 (1.8%), and panTRK (1.8%). HER2/neu amplifications were found in 50% and NTRK translocations were found in 100% of all cases with elevated Her2/neu and panTRK protein expression, respectively.Our data indicate that targeted therapy using e.g., trastuzumab deruxtecan, bicalutamide, pembrolizumab, cetuximab, entrectinib or sacituzumab govitecan might be a promising option especially for a relevant subset of patients with RM-SGC not suitable for salvage surgery. However, evidence from clinical studies regarding response rates to these therapies remains sparse, which underlines the need of multicenter clinical trials.
ISSN:11792000
11771062
DOI:10.1007/s40291-024-00750-w