The clinical impact of testing for biomarkers in gastric cancer patients: a real-world cohort

Karen van der Sluis; Johanna W. van Sandick; Jolanda M. van Dieren; Marieke A. Vollebergh; Cecile Grootscholten; José G. van den Berg; Petur Snaebjornsson; Koen J. Hartemink; Alexander A.F.A. Veenhof; Myriam Chalabi; Liudmila L. Kodach

doi:10.1111/his.14869

The clinical impact of testing for biomarkers in gastric cancer patients: a real-world cohort

Karen van der Sluis, Johanna W. van Sandick, Jolanda M. van Dieren, Marieke A. Vollebergh, Cecile Grootscholten, José G. van den Berg, Petur Snaebjornsson, Koen J. Hartemink, Alexander A.F.A. Veenhof, Myriam Chalabi, Liudmila L. Kodach^*

^*Corresponding author for this work

Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Background and aims: In gastric cancer (GC), HER2 was the first biomarker for guided therapy registered for clinical use. Considering the recent approvals of immune check-point blockade (ICB) in gastro-oesophageal cancers, testing for mismatch repair deficiency (dMMR), Epstein–Barr virus (EBV) and PD-L1 combined positive score (CPS) is becoming increasingly important. Here we describe a real-world cohort on biomarker assessment in GC patients. Methods: Patients diagnosed with GC between 2017 and 2021 were included. Biomarker results were retrieved from electronic patient files. PD-L1 CPS was determined retrospectively on dMMR and EBV-positive (EBV+) tumours. Data on genomic sequencing were analysed separately. Results: Of 363 patients identified, 45% had metastatic disease. In 335 patients (92%) at least one biomarker was tested. The prevalence of HER2+, dMMR and EBV+ tumours was 10% (32 of 319), 7% (20 of 294) and 1% (three of 235), respectively. Of the dMMR and EBV+ tumours, 95% had a PD-L1 CPS ≥ 5. Therapeutic strategy was adjusted in 31 of 55 patients and consisted of anti-HER2 therapies as well as ICB in clinical trials. Genomic alterations were found in 44 of 60 tested patients. TP53 (73%) and PIK3CA (20%) mutations were most common, followed by KRAS mutations (11%) and amplifications (11%). Conclusions: In this real-world cohort, testing for HER2, dMMR and EBV status affected treatment decisions in 56% of the patients. Although most dMMR and EBV+ tumours had a PD-L1 CPS ≥ 5, not all patients with a high probability of treatment response are identified. Based on these results, a stepwise diagnostic strategy is proposed.

Original language	English
Pages (from-to)	826-836
Number of pages	11
Journal	Histopathology
Volume	82
Issue number	6
DOIs	https://doi.org/10.1111/his.14869
Publication status	E-pub ahead of print - 24 Jan 2023

Bibliographical note

Funding Information:
This research was supported by an institutional grant of the Dutch Cancer Society and of the Dutch Ministry of Health, Welfare and Sport.

Publisher Copyright:
© 2023 John Wiley & Sons Ltd.

Other keywords

gastric cancer
immunotherapy
mismatch repair deficiency
PD-L1 CPS
predictive biomarkers
Stomach Neoplasms/genetics
Humans
Epstein-Barr Virus Infections/complications
Retrospective Studies
B7-H1 Antigen/genetics
Herpesvirus 4, Human/genetics
Biomarkers, Tumor/genetics

Access to Document

10.1111/his.14869

Cite this

van der Sluis, K., van Sandick, J. W., van Dieren, J. M., Vollebergh, M. A., Grootscholten, C., van den Berg, J. G., Snaebjornsson, P., Hartemink, K. J., Veenhof, A. A. F. A., Chalabi, M., & Kodach, L. L. (2023). The clinical impact of testing for biomarkers in gastric cancer patients: a real-world cohort. Histopathology, 82(6), 826-836. Advance online publication. https://doi.org/10.1111/his.14869

@article{d326daf142534ffc9b39d4d47de0e912,

title = "The clinical impact of testing for biomarkers in gastric cancer patients: a real-world cohort",

abstract = "Background and aims: In gastric cancer (GC), HER2 was the first biomarker for guided therapy registered for clinical use. Considering the recent approvals of immune check-point blockade (ICB) in gastro-oesophageal cancers, testing for mismatch repair deficiency (dMMR), Epstein–Barr virus (EBV) and PD-L1 combined positive score (CPS) is becoming increasingly important. Here we describe a real-world cohort on biomarker assessment in GC patients. Methods: Patients diagnosed with GC between 2017 and 2021 were included. Biomarker results were retrieved from electronic patient files. PD-L1 CPS was determined retrospectively on dMMR and EBV-positive (EBV+) tumours. Data on genomic sequencing were analysed separately. Results: Of 363 patients identified, 45% had metastatic disease. In 335 patients (92%) at least one biomarker was tested. The prevalence of HER2+, dMMR and EBV+ tumours was 10% (32 of 319), 7% (20 of 294) and 1% (three of 235), respectively. Of the dMMR and EBV+ tumours, 95% had a PD-L1 CPS ≥ 5. Therapeutic strategy was adjusted in 31 of 55 patients and consisted of anti-HER2 therapies as well as ICB in clinical trials. Genomic alterations were found in 44 of 60 tested patients. TP53 (73%) and PIK3CA (20%) mutations were most common, followed by KRAS mutations (11%) and amplifications (11%). Conclusions: In this real-world cohort, testing for HER2, dMMR and EBV status affected treatment decisions in 56% of the patients. Although most dMMR and EBV+ tumours had a PD-L1 CPS ≥ 5, not all patients with a high probability of treatment response are identified. Based on these results, a stepwise diagnostic strategy is proposed.",

keywords = "gastric cancer, immunotherapy, mismatch repair deficiency, PD-L1 CPS, predictive biomarkers, Stomach Neoplasms/genetics, Humans, Epstein-Barr Virus Infections/complications, Retrospective Studies, B7-H1 Antigen/genetics, Herpesvirus 4, Human/genetics, Biomarkers, Tumor/genetics",

author = "{van der Sluis}, Karen and {van Sandick}, {Johanna W.} and {van Dieren}, {Jolanda M.} and Vollebergh, {Marieke A.} and Cecile Grootscholten and {van den Berg}, {Jos{\'e} G.} and Petur Snaebjornsson and Hartemink, {Koen J.} and Veenhof, {Alexander A.F.A.} and Myriam Chalabi and Kodach, {Liudmila L.}",

note = "Funding Information: This research was supported by an institutional grant of the Dutch Cancer Society and of the Dutch Ministry of Health, Welfare and Sport. Publisher Copyright: {\textcopyright} 2023 John Wiley & Sons Ltd.",

year = "2023",

month = jan,

day = "24",

doi = "10.1111/his.14869",

language = "English",

volume = "82",

pages = "826--836",

journal = "Histopathology",

issn = "0309-0167",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "6",

}

TY - JOUR

T1 - The clinical impact of testing for biomarkers in gastric cancer patients

T2 - a real-world cohort

AU - van der Sluis, Karen

AU - van Sandick, Johanna W.

AU - van Dieren, Jolanda M.

AU - Vollebergh, Marieke A.

AU - Grootscholten, Cecile

AU - van den Berg, José G.

AU - Snaebjornsson, Petur

AU - Hartemink, Koen J.

AU - Veenhof, Alexander A.F.A.

AU - Chalabi, Myriam

AU - Kodach, Liudmila L.

N1 - Funding Information: This research was supported by an institutional grant of the Dutch Cancer Society and of the Dutch Ministry of Health, Welfare and Sport. Publisher Copyright: © 2023 John Wiley & Sons Ltd.

PY - 2023/1/24

Y1 - 2023/1/24

N2 - Background and aims: In gastric cancer (GC), HER2 was the first biomarker for guided therapy registered for clinical use. Considering the recent approvals of immune check-point blockade (ICB) in gastro-oesophageal cancers, testing for mismatch repair deficiency (dMMR), Epstein–Barr virus (EBV) and PD-L1 combined positive score (CPS) is becoming increasingly important. Here we describe a real-world cohort on biomarker assessment in GC patients. Methods: Patients diagnosed with GC between 2017 and 2021 were included. Biomarker results were retrieved from electronic patient files. PD-L1 CPS was determined retrospectively on dMMR and EBV-positive (EBV+) tumours. Data on genomic sequencing were analysed separately. Results: Of 363 patients identified, 45% had metastatic disease. In 335 patients (92%) at least one biomarker was tested. The prevalence of HER2+, dMMR and EBV+ tumours was 10% (32 of 319), 7% (20 of 294) and 1% (three of 235), respectively. Of the dMMR and EBV+ tumours, 95% had a PD-L1 CPS ≥ 5. Therapeutic strategy was adjusted in 31 of 55 patients and consisted of anti-HER2 therapies as well as ICB in clinical trials. Genomic alterations were found in 44 of 60 tested patients. TP53 (73%) and PIK3CA (20%) mutations were most common, followed by KRAS mutations (11%) and amplifications (11%). Conclusions: In this real-world cohort, testing for HER2, dMMR and EBV status affected treatment decisions in 56% of the patients. Although most dMMR and EBV+ tumours had a PD-L1 CPS ≥ 5, not all patients with a high probability of treatment response are identified. Based on these results, a stepwise diagnostic strategy is proposed.

AB - Background and aims: In gastric cancer (GC), HER2 was the first biomarker for guided therapy registered for clinical use. Considering the recent approvals of immune check-point blockade (ICB) in gastro-oesophageal cancers, testing for mismatch repair deficiency (dMMR), Epstein–Barr virus (EBV) and PD-L1 combined positive score (CPS) is becoming increasingly important. Here we describe a real-world cohort on biomarker assessment in GC patients. Methods: Patients diagnosed with GC between 2017 and 2021 were included. Biomarker results were retrieved from electronic patient files. PD-L1 CPS was determined retrospectively on dMMR and EBV-positive (EBV+) tumours. Data on genomic sequencing were analysed separately. Results: Of 363 patients identified, 45% had metastatic disease. In 335 patients (92%) at least one biomarker was tested. The prevalence of HER2+, dMMR and EBV+ tumours was 10% (32 of 319), 7% (20 of 294) and 1% (three of 235), respectively. Of the dMMR and EBV+ tumours, 95% had a PD-L1 CPS ≥ 5. Therapeutic strategy was adjusted in 31 of 55 patients and consisted of anti-HER2 therapies as well as ICB in clinical trials. Genomic alterations were found in 44 of 60 tested patients. TP53 (73%) and PIK3CA (20%) mutations were most common, followed by KRAS mutations (11%) and amplifications (11%). Conclusions: In this real-world cohort, testing for HER2, dMMR and EBV status affected treatment decisions in 56% of the patients. Although most dMMR and EBV+ tumours had a PD-L1 CPS ≥ 5, not all patients with a high probability of treatment response are identified. Based on these results, a stepwise diagnostic strategy is proposed.

KW - gastric cancer

KW - immunotherapy

KW - mismatch repair deficiency

KW - PD-L1 CPS

KW - predictive biomarkers

KW - Stomach Neoplasms/genetics

KW - Humans

KW - Epstein-Barr Virus Infections/complications

KW - Retrospective Studies

KW - B7-H1 Antigen/genetics

KW - Herpesvirus 4, Human/genetics

KW - Biomarkers, Tumor/genetics

UR - http://www.scopus.com/inward/record.url?scp=85148377676&partnerID=8YFLogxK

U2 - 10.1111/his.14869

DO - 10.1111/his.14869

M3 - Article

C2 - 36694277

AN - SCOPUS:85148377676

SN - 0309-0167

VL - 82

SP - 826

EP - 836

JO - Histopathology

JF - Histopathology

IS - 6

ER -

The clinical impact of testing for biomarkers in gastric cancer patients: a real-world cohort

Abstract

Bibliographical note

Other keywords

Access to Document

Fingerprint

Cite this