Local and central testing for HER2, PD-L1, MSI/MMR, EBV, and CLDN18.2 in advanced gastric cancer: results from the SAPHIR registry☆

Background: Predictive biomarkers guide treatment selection of patients with advanced gastric and gastroesophageal junction adenocarcinoma (GAC/GEJAC). However, real-world data on testing frequencies and prevalence of biomarkers in Europe are limited. Methods: The SAPHIR registry, a prospective, obs...

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Main Authors: K. Potthoff, H. Bläker, T. Dechow, A. Binninger, K. Ringwald, R. de Buhr, E. von der Heyde, M.-O. Zahn, A. Nusch, S. Dörfel, H. Schulz, I. Haffner, A.K. Höhn, A. Monecke, S. Lorenzen, A. Reinacher-Schick, M. Jänicke, F. Lordick
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:ESMO Real World Data and Digital Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2949820125000335
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author K. Potthoff
H. Bläker
T. Dechow
A. Binninger
K. Ringwald
R. de Buhr
E. von der Heyde
M.-O. Zahn
A. Nusch
S. Dörfel
H. Schulz
I. Haffner
A.K. Höhn
A. Monecke
S. Lorenzen
A. Reinacher-Schick
M. Jänicke
F. Lordick
author_facet K. Potthoff
H. Bläker
T. Dechow
A. Binninger
K. Ringwald
R. de Buhr
E. von der Heyde
M.-O. Zahn
A. Nusch
S. Dörfel
H. Schulz
I. Haffner
A.K. Höhn
A. Monecke
S. Lorenzen
A. Reinacher-Schick
M. Jänicke
F. Lordick
author_sort K. Potthoff
collection DOAJ
description Background: Predictive biomarkers guide treatment selection of patients with advanced gastric and gastroesophageal junction adenocarcinoma (GAC/GEJAC). However, real-world data on testing frequencies and prevalence of biomarkers in Europe are limited. Methods: The SAPHIR registry, a prospective, observational cohort study of patients with metastatic GAC/GEJAC, collects longitudinal clinical data, patient-reported outcomes as well as tumor tissue samples from routine diagnostics. Here, we focus on biomarker testing and test results in routine clinical practice. In addition, central pathology assessment was performed for HER2, PD-L1, dMMR/MSI, EBV, and CLDN18.2. Results: From December 2019 until March 2022, a total of 473 evaluable patients were enrolled at 109 study sites in Germany. Their median age was 66.8 years, 73.6% were male, and 76.7% had an ECOG performance status of 0/1. In clinical routine, testing rates for HER2, PD-L1, MSI, EBV, and MMR were 78.6%, 31.3%, 15.6%, 4.9%, and 2.5%, respectively. CLDN18.2 was not tested during the respective period. By central testing, the positivity rates were 11.8% for HER2, 75.2% for PD-L1 (CPS ≥1, TPS/IC ≥1%), 2.5% for dMMR/MSI-H, 0.6% for EBV, and 26.7% for CLDN18.2. Deviations between local and central testing were 12.4% for HER2 and 22.4% for PD-L1. Conclusions: This study provides valuable insights on molecular testing in patients with GAC/GEJAC in Germany. In real-world, patients were frequently tested for actionable alterations, but there is room for improvement. Deviating test results of HER2 and PD-L1 by local and central pathology may reflect limitations in testing methodologies. In addition, these patients might not receive the most effective treatment.
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spelling doaj-art-3b3d3ca0dd7446b3b65afefe2245bdb52025-08-20T03:14:01ZengElsevierESMO Real World Data and Digital Oncology2949-82012025-06-01810014410.1016/j.esmorw.2025.100144Local and central testing for HER2, PD-L1, MSI/MMR, EBV, and CLDN18.2 in advanced gastric cancer: results from the SAPHIR registry☆K. Potthoff0H. Bläker1T. Dechow2A. Binninger3K. Ringwald4R. de Buhr5E. von der Heyde6M.-O. Zahn7A. Nusch8S. Dörfel9H. Schulz10I. Haffner11A.K. Höhn12A. Monecke13S. Lorenzen14A. Reinacher-Schick15M. Jänicke16F. Lordick17iOMEDICO, Freiburg; Correspondence to: Dr. med. Karin Potthoff, iOMEDICO, Ellen-Gottlieb-Straße 19, 79106 Freiburg, Germany. Tel: +49-761-15242-0Institut für Pathologie, Universitätsmedizin Leipzig, LeipzigGemeinschaftspraxis für Hämatologie und Onkologie GbR, RavensburgiOMEDICO, FreiburgiOMEDICO, FreiburgiOMEDICO, FreiburgOnkologische Schwerpunktpraxis, HannoverüBAG/MVZ Onkologische Kooperation Harz GbR, GoslarPraxis für Hämatologie und Internistische Onkologie, RatingenOnkozentrum Dresden/Freiberg, DresdenPraxis Internistischer Onkologie und Hämatologie (PIOH), FrechenMedizinische Klinik II und Universitäres Krebszentrum (UCCL), Comprehensive Cancer Center Central Germany (CCCG), Universitätsmedizin Leipzig, LeipzigInstitut für Pathologie, Universitätsmedizin Leipzig, LeipzigInstitut für Pathologie, Universitätsmedizin Leipzig, LeipzigKlinikum Rechts der Isar der TU München, Klinik und Poliklinik für Innere Medizin III, Hämatologie und Internistische Onkologie, MünchenSt. Josef-Hospital, Ruhr-Universität Bochum, Klinik für Hämatologie und Onkologie mit Palliativmedizin, Bochum, GermanyiOMEDICO, FreiburgMedizinische Klinik II und Universitäres Krebszentrum (UCCL), Comprehensive Cancer Center Central Germany (CCCG), Universitätsmedizin Leipzig, LeipzigBackground: Predictive biomarkers guide treatment selection of patients with advanced gastric and gastroesophageal junction adenocarcinoma (GAC/GEJAC). However, real-world data on testing frequencies and prevalence of biomarkers in Europe are limited. Methods: The SAPHIR registry, a prospective, observational cohort study of patients with metastatic GAC/GEJAC, collects longitudinal clinical data, patient-reported outcomes as well as tumor tissue samples from routine diagnostics. Here, we focus on biomarker testing and test results in routine clinical practice. In addition, central pathology assessment was performed for HER2, PD-L1, dMMR/MSI, EBV, and CLDN18.2. Results: From December 2019 until March 2022, a total of 473 evaluable patients were enrolled at 109 study sites in Germany. Their median age was 66.8 years, 73.6% were male, and 76.7% had an ECOG performance status of 0/1. In clinical routine, testing rates for HER2, PD-L1, MSI, EBV, and MMR were 78.6%, 31.3%, 15.6%, 4.9%, and 2.5%, respectively. CLDN18.2 was not tested during the respective period. By central testing, the positivity rates were 11.8% for HER2, 75.2% for PD-L1 (CPS ≥1, TPS/IC ≥1%), 2.5% for dMMR/MSI-H, 0.6% for EBV, and 26.7% for CLDN18.2. Deviations between local and central testing were 12.4% for HER2 and 22.4% for PD-L1. Conclusions: This study provides valuable insights on molecular testing in patients with GAC/GEJAC in Germany. In real-world, patients were frequently tested for actionable alterations, but there is room for improvement. Deviating test results of HER2 and PD-L1 by local and central pathology may reflect limitations in testing methodologies. In addition, these patients might not receive the most effective treatment.http://www.sciencedirect.com/science/article/pii/S2949820125000335biomarkergastric cancerHER2PD-L1real-world datatest deviation
spellingShingle K. Potthoff
H. Bläker
T. Dechow
A. Binninger
K. Ringwald
R. de Buhr
E. von der Heyde
M.-O. Zahn
A. Nusch
S. Dörfel
H. Schulz
I. Haffner
A.K. Höhn
A. Monecke
S. Lorenzen
A. Reinacher-Schick
M. Jänicke
F. Lordick
Local and central testing for HER2, PD-L1, MSI/MMR, EBV, and CLDN18.2 in advanced gastric cancer: results from the SAPHIR registry☆
ESMO Real World Data and Digital Oncology
biomarker
gastric cancer
HER2
PD-L1
real-world data
test deviation
title Local and central testing for HER2, PD-L1, MSI/MMR, EBV, and CLDN18.2 in advanced gastric cancer: results from the SAPHIR registry☆
title_full Local and central testing for HER2, PD-L1, MSI/MMR, EBV, and CLDN18.2 in advanced gastric cancer: results from the SAPHIR registry☆
title_fullStr Local and central testing for HER2, PD-L1, MSI/MMR, EBV, and CLDN18.2 in advanced gastric cancer: results from the SAPHIR registry☆
title_full_unstemmed Local and central testing for HER2, PD-L1, MSI/MMR, EBV, and CLDN18.2 in advanced gastric cancer: results from the SAPHIR registry☆
title_short Local and central testing for HER2, PD-L1, MSI/MMR, EBV, and CLDN18.2 in advanced gastric cancer: results from the SAPHIR registry☆
title_sort local and central testing for her2 pd l1 msi mmr ebv and cldn18 2 in advanced gastric cancer results from the saphir registry☆
topic biomarker
gastric cancer
HER2
PD-L1
real-world data
test deviation
url http://www.sciencedirect.com/science/article/pii/S2949820125000335
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