The information contained in the site is intended for US healthcare professionals only. By selecting “Okay” below, you verify that you are a licensed US healthcare professional.
By selecting "Okay" below, you verify that you are a licensed US healthcare professional.
Despite a landscape clouded in complexity, emerging biomarkers are expanding our view of patient populations, and biomarker testing could provide a more comprehensive patient profile.
CLDN18.2=Claudin18.2; FGFR2b=fibroblast growth factor receptor 2b; HER2=human epidermal growth factor receptor 2b; MSI=microsatellite instability; PD-L1=programmed death-ligand 1.
AN UNMET NEED
In the United States, approximately 6% of patients with metastatic gastric
cancer (mGC) survive 5 years post diagnosis.1,2*
*US SEER 18 areas (2011–2017), distant stomach cancer.1,2
IN THE UNITED STATES
In 2022, it is estimated that nearly 26,400 new cases of G/GEJ cancers will be diagnosed in the US, of which 62% will likely be advanced† stage disease.1,2
In the US, patients with advanced disease at diagnosis will likely have a poor outcome, as less than 50% receive second-line therapy for mGC.3,4
†Locally advanced (stage II and III) and metastatic (stage IV) gastric/GEJ cancer per TNM staging classification as described in NCCN Guidelines®.4
AROUND THE WORLD
Over 1 million new cases of G/GEJ cancers were diagnosed worldwide in 2020, making it the 5th most diagnosed cancer.5
An estimated 769,000 people died worldwide in 2020 due to G/GEJ cancers, making it the 4th most deadly cancer.5
In 2018, the global overall 5-year survival rate was
approximately ≤10% in mGC.6
help identify previously undefined subsets of mG/GEJ cancer patients:
are used to inform clinical decisions:
Emerging and established biomarkers can be detected by standard IHC staining methods.
‡FGFR2b overexpression can be determined by IHC; FGFR2 gene amplification can be determined by ctDNA.17
IHC, ISH, NGS4,18||
IHC=immunohistochemistry; ctDNA=circulating tumor DNA; ISH=in situ hybridization; NGS=next generation sequencing; PCR=polymerase chain reaction.
§Varying diagnostic assays.19
||Other ISH methods (FISH=fluorescent ISH; SISH=silver ISH; CISH=chromogenic ISH; DDISH=dual-color dual-hapten ISH).18
Emerging biomarkers are highly prevalent among mG/GEJ biomarkers.
Biomarker prevalence estimates from select studies are reported below. Prevalence data can vary among studies due to tumor heterogeneity, differences in patient population, clinical trial methodology, and diagnostic assays used.13,20-22
¶2+/3+ IHC staining in ≥75% of tumor cells.20
(Variable due to multiple factors)#
CPS ≥1: 67-73%
CPS ≥5: 29-31%
CPS ≥10: 16-18%
CPS=combined positive score.
#PD-L1 prevalence of PD-L1 at various CPS thresholds is still being explored. Data are from a randomized controlled trial and a real-world retrospective medical records study.22,23
Claudins are a family of transmembrane proteins7,26:
Claudins are a major component of epithelial and endothelial tight junctions, which are involved in controlling the flow of molecules between cells.7-9
Claudins are present throughout the body, but two specific isoforms of CLDN18 are localized to certain tissue types7,26:
Preclinical studies have shown that CLDN18.2 may become more exposed and accessible to antibodies as gastric tumors develop.7,27,28
CONFINED IN HEALTHY TISSUE
In gastric epithelial cells, CLDN18.2 is typically buried in the tight junction supramolecular complex.7,9,28
It functions to regulate selective barrier properties and contribute to cell-to-cell epithelial adhesion.7-10
EXPOSED TO ANTIBODIES IN TUMORIGENESIS
Malignant transformation leads to polarity disruptions and structure loss.27,28 As a result, CLDN18.2 may be more exposed and accessible to antibodies.7,27,28
RETAINED DURING TRANSFORMATION
The presence of CLDN18.2 is retained throughout malignant transformation, both in the primary tumor site and metastatic disease.7,27
CLDN18.2 may be expressed when tumors develop in esophageal, pancreatic, lung, and ovarian tissues as well.7
While approximately 70% of mG/GEJ cancers express CLDN18.2 (at any level), recent studies have shown approximately 36% of mG/GEJ patients are CLDN18.2 positive (high expression).20
When evaluating the relationship between CLDN18.2 and other biomarkers, data suggests there is limited overlap.
*Study population was limited to 350 Caucasian patients with mG/GEJ cancer, of which 117 patients had high expression of CLDN18.2. FGFR2b was not evaluated in this study.20
CLDN18.2 is expressed in both diffuse- type tumors and intestinal-type tumors.16
FGFR signaling contributes to tumor progression by enhancing angiogenesis and proliferation.11
FGFR2b positivity has been observed in 30% of mG/GEJ cancers.21
FGFR2b positivity: overexpression (IHC) and/or gene amplification (ctDNA)
Detecting FGFR2b overexpression can be done with the following tests.17
HER2 (human epidermal growth factor receptor 2) is a receptor-tyrosine kinase that is overexpressed and/or amplified in mG/GEJ cancer.11
HER2 is a proto-oncogene that is involved in signaling pathways, which leads to cell growth and differentiation.18
HER2 positivity has been reported in 22% of advanced G/GEJ cancers.13
HER2 positivity: overexpression (IHC3+) and/or gene amplification (FISH positive)
Detection of HER2 may be done with IHC, ISH methods and NGS, and is generally more associated with the intestinal type.4,13,18*
*IHC/ISH should be considered first, followed by additional NGS testing as appropriate.4
MSI is associated with genomic instability and increased susceptibility to tumor development.11
Microsatellites are repeated sequences of nucleotides in DNA.14
MSI-H has been reported in 4% of mG/GEJ cancers.24
Detection of MSI is typically assessed with various methods.4
PD-L1 (programmed death-ligand 1) is a transmembrane protein that may be expressed on various tumor cells and/or immune cells.35
Prevalence of PD-L1 has been reported for several positivity thresholds throughout various studies: 67-73% CPS ≥1, 29-31% CPS ≥5, and 16-18% CPS ≥10.22,23*+
*Study population was limited to 592 patients with locally advanced or metastatic mG/GEJ cancer who experienced disease progression after first-line therapy with a platinum and fluoropyrimidine.23
+Study analyzed 56 specimens from therapy-naive biopsies or post-neoadjuvant treatment from German patients with primarily non-metastatic gastric adenocarcinoma.22
PD-L1 expression is detected using IHC.4
NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer (NCCN Guidelines®) support using biomarkers to help map the path forward for patients.4
The NCCN Guidelines® recommend:
Biomarker testing provides more insight into mG/GEJ cancer as more biomarkers are discovered.
*IHC/ISH should be considered first, followed by additional NGS testing as appropriate.4
As biomarker research continues, it expands our view of the patient population, reveals more information about the mG/GEJ cancer landscape, and helps inform clinical decisions.
Have a question?
Find answers at
Download a PDF about the biomarker advancements in mG/GEJ cancers.
Stay up to date.
By signing up below, you will receive updates about emerging biomarkers in mG/GEJ cancer. You may also be contacted by an Astellas representative. Please note that fields marked with (*) are required.
You will now receive email updates about emerging biomarkers in mG/GEJ cancer, and
you may be contacted by an Astellas representative.
The information provided on gastriccancerbiomarkers.com is intended for residents of the United States.
© 2022 Astellas Pharma US, Inc. All rights reserved.
ATTENTION: PLEASE READ THESE TERMS CAREFULLY BEFORE USING THIS WEBSITE GASTRICANCERBIOMARKERS.COM. BY USING THIS SITE, INCLUDING ANY SERVICES PROVIDED ON OR THROUGH THIS SITE GASTRICANCERBIOMARKERS.COM, YOU INDICATE THAT YOU ACCEPT THESE TERMS. IF YOU DO NOT ACCEPT THESE TERMS, DO NOT USE THIS SITE.
GENERAL INFORMATION. This Site contains information that may be of interest to members of the healthcare community. Please feel free to browse this Site and Services. Your access and use of the Site are subject to the following terms and conditions, and all applicable laws. By accessing and browsing this Site and Services, you accept, without limitation or qualification, these terms and conditions and acknowledge that they supersede any other agreement between you and Astellas.
SITE CONTENT. All material on the Site including, but not limited to, text, images, graphics, documents, audio, or video (collectively, the Site Content) are protected under applicable copyright laws. You may copy, download, or print Site Content for your personal, noncommercial purposes only, but no modification or further reproduction of content is permitted. The Site Content may not otherwise be copied, downloaded, reproduced, deleted, modified, republished, retransmitted, displayed, or used to create derivative works without the express written permission of Astellas.
Trademarks, service marks, trade dress, logos, designs, and slogans appearing on this Site are owned by Astellas, its Affiliate companies, its licensors, or its partners, and may not be used for advertising or publicity purposes, or to indicate any affiliation with or endorsement by Astellas, except with the express written permission of Astellas.
Nothing contained in this Site should be construed as granting a license to, or right in, any trademarks, patents, or copyrights of Astellas, or any other party.
The content or material Astellas provides through the Site is for informational purposes only. Nothing on this Site should be construed as the giving of advice (medical, legal, financial, investment, or other professional advice) or the making of a recommendation, and information on the Site should not be relied on as the basis for any decision or action. IT IS IMPORTANT THAT YOU RELY ONLY ON THE ADVICE OF A HEALTHCARE PROFESSIONAL TO ADVISE YOU ON YOUR SPECIFIC SITUATION. YOU SHOULD NEVER DISREGARD OR DELAY SEEKING MEDICAL ADVICE BECAUSE OF SOMETHING THAT YOU HAVE SEEN ON THIS SITE.
OBLIGATIONS OF SITE VISITORS OR USERS. You agree not to do any of the following while visiting or using the Site or any services provided by or through this Site:
LINKS TO OTHER WEBSITES. Solely as a convenience to you, Astellas may provide links on this Site to other websites that are not maintained by or under the control of Astellas. If you use these links, you will leave this Site. Please remember that linked sites are not necessarily Astellas's sites, and the information could change without Astellas's knowledge. Third-party linked sites and their contents should not be attributed to Astellas (or any of its affiliated companies) in any manner. Astellas has not attempted to verify the truth or accuracy of any third-party sites or content contained on any third-party sites and does not make any representations or warranties about such sites or the content of such sites. If you decide to access any of the third-party sites linked to this Site, you do so entirely at your own risk. In the event Astellas endorses a particular organization, Astellas will clearly state its endorsement next to any link to that organization.
DISCLAIMER OF WARRANTIES. THIS SITE, INCLUDING ANY INFORMATION, SERVICES, OR MATERIAL MADE AVAILABLE ON OR THROUGH THIS SITE, IS PROVIDED ON AN "AS IS" AND "AS AVAILABLE" BASIS. TO THE MAXIMUM EXTENT PERMITTED BY LAW, ASTELLAS EXPRESSLY DISCLAIMS ALL WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING WITHOUT LIMITATION ANY WARRANTY OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, OR NONINFRINGEMENT. FURTHERMORE, ASTELLAS DOES NOT WARRANT THE ACCURACY OR COMPLETENESS OF ANY INFORMATION ON THIS SITE AND MAY MAKE CHANGES TO THE INFORMATION, SERVICES, OR MATERIAL MADE AVAILABLE ON OR THROUGH THIS SITE AT ANY TIME WITHOUT PRIOR NOTICE TO USERS OF THIS SITE. INFORMATION AT THIS SITE THAT IS PERIODICALLY UPDATED MAY NOT BE CURRENT AT THE MOMENT YOU VISIT THIS SITE AND MAY CONTAIN ERRORS. ASTELLAS MAKES NO WARRANTY THAT THE SITE WILL MEET YOUR REQUIREMENTS; THAT THE SITE WILL BE UNINTERRUPTED, TIMELY, SECURE, OR ERROR-FREE; THAT MESSAGES OR REQUESTS WILL BE DELIVERED; THAT DEFECTS WILL BE CORRECTED; OR THAT THIS SITE IS FREE OF VIRUSES OR OTHER HARMFUL COMPONENTS. ASTELLAS MAKES NO WARRANTY REGARDING ANY GOODS OR SERVICES PURCHASED OR OBTAINED THROUGH THE SITE OR ANY TRANSACTIONS ENTERED INTO THROUGH THE SITE. YOU ASSUME THE ENTIRE RISK AS TO THE RESULTS AND PERFORMANCE OF THE SITE AND ANY GOODS OR SERVICES PURCHASED THEREFROM.
LIMITATION OF LIABILITY. IN NO EVENT WILL ASTELLAS BE LIABLE FOR ANY DAMAGES WHATSOEVER. THIS INCLUDES BUT IS NOT LIMITED TO DIRECT, INDIRECT, INCIDENTAL, PUNITIVE, AND CONSEQUENTIAL DAMAGES (INCLUDING, WITHOUT LIMITATION, THOSE RESULTING FROM LOST PROFITS, LOST DATA, OR BUSINESS INTERRUPTION) ARISING OUT OF THE USE, INABILITY TO USE, OR THE RESULT OF USE OF THIS SITE, ANY WEBSITES LINKED TO THIS SITE, THE MATERIALS OR INFORMATION CONTAINED ON ANY OR ALL SUCH SITES, OR ANY MATERIALS, PRODUCTS, OR SERVICES OFFERED ON THIS SITE OR SITES LINKED TO THIS SITE, WHETHER BASED ON WARRANTY, CONTRACT, TORT, OR ANY OTHER LEGAL THEORY AND WHETHER OR NOT ADVISED ON THE POSSIBILITY OF SUCH DAMAGES. IN NO EVENT WILL ASTELLAS, ITS SUPPLIERS, OR ANY OTHER PARTY INVOLVED IN CREATING, PRODUCING, OR DELIVERING THIS SITE BE LIABLE TO YOU IN ANY MANNER WHATSOEVER FOR ANY DECISION MADE OR ACTION OR NONACTION TAKEN BY YOU IN RELIANCE UPON INFORMATION PROVIDED THROUGH THIS SITE. APPLICABLE LAW MAY NOT ALLOW THE EXCLUSION OR LIMITATION OF INCIDENTAL OR CONSEQUENTIAL DAMAGES, SO THE ABOVE LIMITATION OR EXCLUSION MAY NOT APPLY TO YOU.
THIS SITE IS INTENDED FOR US AUDIENCES ONLY. Access to and use of this Site is subject to the above terms and conditions. This Site was developed and is maintained by Astellas. Information, copy, and claims are intended only for the residents of the United States.