FGFR2b is an emerging protein biomarker overexpressed in 20%–30% of gastric/GEJ cancers, as detected by IHC1,2,*
ABOUT GASTRIC CANCER
Gastric cancer is the 5th most common cancer and the 5th leading cause of cancer-related death worldwide3
61%
of patients with gastric cancer have advanced disease† at the time of diagnosis4
5-year relative survival rates by stage at diagnosis from 2014 to 20204,‡
Distantly metastatic cancers have a survival rate 5x lower than regional gastric cancers, and 10x lower than localized gastric cancers4,‡
*Approximate range from a phase 2 trial in locally advanced or metastatic gastric/GEJ cancer patients. Of 910 prescreened patients, 274 (30%) were positive for FGFR2b with any 2+/3+ tumor cell staining by IHC. 155 of the any 2+/3+ positives underwent further testing with 98 (63%) exhibiting FGFR2b ≥ 10% 2+/3+ tumor cell staining by IHC; 63% extrapolated to the 274 any 2+/3+ positives estimates to ~20%.1,5
†This includes patients with regional disease, or those whose cancer has spread to regional lymph nodes, and metastatic disease at the time of diagnosis. There are 26,890 estimated new cases.4
‡Assessed between 2014 and 2020 in the United States.4
1L, first line; FGFR2b, fibroblast growth factor receptor 2, isoform IIIb; GEJ, gastroesophageal junction; IHC, immunohistochemistry.
GASTRIC CANCER BIOMARKERS
Gastric/GEJ cancers are complex and heterogeneous diseases characterized by the expression of certain biomarkers, including:2,6,7
Receptor tyrosine kinases
Tight junction protein
Immune-related markers
As the biomarker landscape continues to evolve, it may inform advancements in precision medicine2
CLDN18.2, claudin-18 isoform 2; dMMR, deficient mismatch repair; FGFR2b, fibroblast growth factor receptor 2, isoform IIIb; HER2, human epidermal growth factor receptor 2; MSI-H, microsatellite instability-high; PD-L1, programmed cell death ligand 1.
FGFR2b PROTEIN OVEREXPRESSION
FGFR2b protein overexpression is an emerging biomarker prevalent in 20%–30% of patients with advanced gastric/GEJ cancer1,5,*
Overexpression of FGFR2b protein drives tumorigenesis8,9
FGFR2b drives multiple cellular functions8,9
FGFR2b protein overexpression may be prognostic and associated with shorter survival in gastric/GEJ cancers11
*Approximate range from a phase 2 trial in locally advanced or metastatic G/GEJ cancer patients. Of 910 prescreened patients, 274 (30%) were positive for FGFR2b with any 2+/3+ tumor cell staining by IHC. 155 of the any 2+/3+ positives underwent further testing with 98 (63%) exhibiting FGFR2b ≥ 10% 2+/3+ tumor cell staining by IHC; 63% extrapolated to the 274 of the any 2+/3+ positives estimates to ~20%.1,5
AKT, protein kinase B; CBL, Casitas B lineage lymphoma; FGF, fibroblast growth factor; FGFR2b, fibroblast growth factor receptor 2, isoform IIIb; FRS2a, FGFR substrate 2a; GAB1, GRB2-associated-binding protein 1; GEJ, gastroesophageal junction; GRB2, growth factor receptor-bound 2; Ig, immunoglobulin; IHC, immunohistochemistry; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; MKP1, mitogen-activated protein kinase phosphatase 1; MKP3, mitogen-activated protein kinase phosphatase 3; P, phosphate; PI3K, phosphoinositide 3-kinase; PI3K-AKT, phosphoinositide 3-kinase Akt protein kinase B; RaF, proto-oncogene, serine/threonine kinase; RAS, rat sarcoma; RAS-MAPK, rat sarcoma mitogen-activated protein kinase; RTK, receptor tyrosine kinase; SEFB, S-adenosyl methionine-dependent methyltransferase; SoS, son of sevenless; SPRY, sprouty protein; TM, transmembrane.
BIOMARKER DETECTION CONSIDERATIONS FOR GASTRIC CANCER
Similar to other gastric/GEJ cancer biomarkers, FGFR2b protein overexpression can be detected by IHC2,§
Emerging
Actionable
FGFR2b protein overexpression is defined as tumor cells with moderate (2+) to strong (3+) membranous staining1,16
§Roche Diagnostics has created the VENTANA® FGFR2b (FPR2-D) Mouse Monoclonal Antibody assay (Class 1) that recognizes the FGFR2b isoform via IHC.17,18
CLDN18.2, claudin-18 isoform 2; dMMR, deficient mismatch repair; FGFR2b, fibroblast growth factor receptor 2, isoform IIIb; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ISH, in situ hybridization; MSI-H, microsatellite instability-high; NGS, next-generation sequencing; PCR, polymerase chain reaction; PD-L1, programmed cell death ligand 1.
RESOURCES
Watch the FGFR2b DSE video
The clinical impact of targeting FGFR2b in 1L gastric/GEJ cancer is being evaluated. Amgen is committed to exploring the full potential of FGFR2b as an emerging biomarker2,19
1L, first line; DSE, disease state education; GEJ, gastroesophageal junction; FGFR2b, fibroblast growth factor receptor 2, isoform IIIb.
References: 1. Wainberg ZA, et al. Gastric Cancer. 2024;27:558-570. 2. Sato Y, et al. J Clin Med. 2023;12:4646. 3. Bray F, et al. CA Cancer J Clin. 2024;74:229-263. 4. National Cancer Institute. https://seer.cancer.gov/statfacts/html/stomach.html. Accessed January 21, 2025.
5. Wainberg ZA, et al. Lancet Oncol. 2022;23:1430-1440. 6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Gastric Cancer V.5.2024. ©National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed January 2, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric Junction Cancers V.5.2024. ©National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed January 2, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
8. Khosravi F, et al. Front Cell Dev Biol. 2021;9:672935. 9. Turner N, et al. Nat Rev Cancer. 2010;10:116-129. 10. Ishiwata T. Front Biosci (Landmark Ed). 2018;23:626-639. 11. Ahn S, et al. Mod Pathol. 2016;29:1095-1103. 12. Han N, et al. Pathobiology. 2015;82:269-279. 13. Zhang J, et al. Cells. 2019;8:637. 14. Krook MA, et al. Br J Cancer. 124:880-892. 15. Catenacci D, et al. Presented at: American Society of Clinical Oncology Annual Meeting; June 4, 2021–June 8, 2021; Chicago, IL. Abstract 4010. 16. Data on file, Amgen 2021. 17. Roche Diagnostics. https://elabdoc-prod.roche.com/eLD/api/downloads/65a1283e-a4f6-ee11-2591-005056a71a5d?countryIsoCode=XG. Accessed November 27, 2024. 18. FDA.gov. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/rl.cfm? lid=516262&lpcd=NJT. Accessed November 27, 2024. 19. Wainberg ZA, et al. Presented at: American Society of Clinical Oncology Gastrointestinal Cancers Symposium; January 15, 2021-January 18, 2021; Chicago, IL. Abstract LBA160.