FGFR2b is an emerging protein biomarker overexpressed in 20%–30% of G/GEJ cancers, as detected by IHC.1,2,*
ABOUT GASTRIC CANCER
Gastric cancer is the fifth most common cancer and the fifth 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,‡
The 5-year relative survival rate for patients with distantly metastatic gastric cancer at diagnosis is only 7% in the United States‡
*Approximate range based on 910 prescreened patients for a phase 2 trial in locally advanced or metastatic G/GEJ cancer, of which 274 patients (30%) were prescreened positive for FGFR2b any 2+/3+ tumor cell staining by IHC, and on the 155 enrolled patients, of which 96 (62%) exhibited FGFR2b ≥ 10% 2+/3+ tumor cell staining by IHC.1
†This includes patients with regional disease, or those whose cancer have 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; G/GEJ, gastric/gastroesophageal junction; IHC, immunohistochemistry.
GASTRIC CANCER BIOMARKERS
Gastric cancer is a complex and heterogeneous disease characterized by the expression of certain biomarkers including HER2, PD-L1, MSI-H/dMMR, CLDN18.2, and FGFR2b2,5
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 G/GEJ cancer1,*
Overexpression of FGFR2b protein drives tumorigenesis6,7
FGFR2b drives multiple cellular functions6,7
FGFR2b protein overexpression may be prognostic and associated with shorter survival in G/GEJ cancers9
*Approximate range based on the 910 prescreened patients for a phase 2 trial in locally advanced or metastatic G/GEJ cancer, of which 274 patients (30%) were prescreened positive for FGFR2b any 2+/3+ tumor cell staining by IHC, and on the 155 enrolled patients, of which 96 patients (62%) exhibited FGFR2b ≥ 10% 2+/3+ tumor cell staining by IHC.1
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; G/GEJ, gastric/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 cancer biomarkers, FGFR2b protein overexpression can be detected by IHC, a method to evaluate protein expression2,§
Emerging
Actionable
FGFR2b protein overexpression by IHC is defined as 2+/3+ staining10
§Currently, FGFR2b testing is in the context of investigational clinical trials with no approved diagnostic test in the market.2
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
FGFR2b in Gastric
Cancer Factsheet
Gastric Cancer
Booklet
FGFR2b
Deck
The impact of targeting FGFR2b in first-line G/GEJ cancer is being evaluated. Amgen is committed to exploring the full potential of FGFR2b as an emerging biomarker2,11
DSE, disease state education; G/GEJ, gastric/gastroesophageal junction; FGFR2b, fibroblast growth factor receptor 2, isoform IIIb.
References: 1. Wainberg ZA, Enzinger PC, Kang Y-K, et al. Lancet Oncol. 2022;23:1430-1440. 2. Sato Y, Okamoto K, Kawano Y, et al. Novel biomarkers of gastric cancer: Current research and future perspectives. J Clin Med. 2023;12:4646. 3. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024. doi:10.3322/caac.21834. 4. National Cancer Institute. https://cancerstatisticscenter.cancer.org. Accessed April 3, 2024. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Gastric Cancer V.1.2024. ©National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed March 24, 2024. 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. 6. Khosravi F, Ahmadvand N, Bellusci S, et al. The multifunctional contribution of FGF signaling to cardiac development, homeostasis, disease and repair. Front Cell Dev Biol. 2021;9:672935. 7. Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010;10:116-129. 8. Ishiwata T. Role of fibroblast growth factor receptor-2 splicing in normal and cancer cells. Front Biosci (Landmark Ed). 2018;23:626-639. 9. Ahn S, Lee J, Hong M, et al. FGFR2 in gastric cancer: protein overexpression predicts gene amplification and high H-index predicts poor survival. Mod Pathol. 2016;29:1095-1103. 10. Catenacci D. Slides presented at: American Society of Clinical Oncology Annual Meeting; June 2021; Chicago, IL. Abstract 4010. 11. Wainberg ZA, Enzinger P, Kang Y-K, et al. Slides presented at: American Society of Clinical Oncology Gastrointestinal Cancers Symposium; January, 2021; Online Virtual Scientific Program. Abstract LBA160.