Comprehensive biomarker analysis of long-term response to trastuzumab in patients with HER2-positive advanced gastric or gastroesophageal adenocarcinoma
Background - A subgroup of patients with HER2-positive metastatic gastric and gastroesophageal junction cancers shows long-term response under trastuzumab maintenance monotherapy. Obviously, HER2 status alone is not able to identify these patients. We performed this study to identify potential new p...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
April 2023
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| In: |
European journal of cancer
Year: 2023, Volume: 183, Pages: 119-130 |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2023.01.022 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ejca.2023.01.022 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0959804923000461 
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| Author Notes: | Isabel Porth, Daniela Hirsch, Yonca Ceribas, Philip Weidner, Wilko Weichert, Thorsten Oliver Götze, Sven Perner, Kim Luley, Christian Moritz Heyer, Carolina de la Torre, Ralf-Dieter Hofheinz, Sylvie Lorenzen, Timo Gaiser |
| Summary: | Background - A subgroup of patients with HER2-positive metastatic gastric and gastroesophageal junction cancers shows long-term response under trastuzumab maintenance monotherapy. Obviously, HER2 status alone is not able to identify these patients. We performed this study to identify potential new prognostic biomarkers for this long-term responding patient group. - Patients and methods - Tumour samples of 19 patients with HER2-positive metastatic gastric and gastroesophageal junction cancer who underwent trastuzumab treatment were retrospectively collected from multiple centres. Patients were divided into long-term responding (n = 7) or short-term responding group (n = 12) according to progression-free survival (PFS≥12 months vs. PFS < 12 months). Next-generation sequencing and microarray-based gene expression analysis were performed along with HER2 and PD-L1 immunohistochemistry. - Results - Long-term responding patients had significantly higher PD-L1 combined positive scores (CPS) and CPS correlated with longer progression-free survival. PD-L1 positivity (CPS ≥ 1) was further associated with an increased CD4+ memory T-cell score. The ERBB2 copy number as well as the tumour mutational burden could not discriminate between short-term and long-term responding patients. Genetic alterations and coamplifications in HER2 pathway associated genes such as EGFR, which were connected to trastuzumab resistance, were present in 10% of the patients and equally distributed between the groups. - Conclusion - The study highlights the clinical relevance of PD-L1 testing also in the context of trastuzumab treatment and offers a biological rational by demonstrating elevated CD4+ memory T-cells scores in the PD-L1-positive group. |
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| Item Description: | Gesehen am 19.05.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2023.01.022 |