{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:15:01Z","timestamp":1783401301035,"version":"3.54.6"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Patients with gastric cancer (GC) harboring fibroblast growth factor receptor 2 (FGFR2) amplification showed significantly worse survival, compared with patients with FGFR2-unamplified GC. Although various targeted drugs have been developed, previous studies have shown that their efficacy remains suboptimal in most patients within this subgroup. We retrospectively present two cases of FGFR2-amplified advanced GC treated with FGFR inhibitors. Case 1 was a 52-year-old female diagnosed with stage IVB (cTxN+M1, bone and lymph node metastases, HER2-negative, CPS\u00a0=\u00a02) poorly differentiated signet-ring cell carcinoma, harboring high-level FGFR2 amplification (gene copy number=24.7). Due to extensive bone metastases resulting in severe anemia, pain, and limited mobility (performance status 3), the patient was intolerant to chemotherapy and immunotherapy. In the first-line setting, she received pemigatinib, achieving a progression-free survival (PFS) of 4.4 months and an overall survival (OS) of 8.3 months, accompanied by a significant decrease in tumor markers and rapid clinical symptom improvement. Case 2 was a 61-year-old female diagnosed with stage IVB (cT4bN+M1, liver and lymph node metastases, HER2-negative, CPS\u00a0=\u00a05) poorly differentiated adenocarcinoma. In the third-line setting, she received infigratinib, attaining a PFS of 5.7 months and an OS of 18.5 months. Both patients experienced predictable and manageable FGFR inhibitor-related adverse events (e.g., keratitis, onychotoxicity, hyperphosphatemia). This case series offers hypothesis-generating observations suggesting potential activity of FGFR inhibitors (such as pemigatinib and infigratinib) in patients with FGFR2-amplified advanced gastric cancer who have limited conventional therapeutic options or are intolerant to chemotherapy, highlighting the importance of next-generation sequencing-guided precision therapy.<\/jats:p>","DOI":"10.3389\/fonc.2026.1828167","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:23:32Z","timestamp":1783398212000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical response to FGFR inhibitors in patients with FGFR2-amplified advanced gastric cancer: two case reports"],"prefix":"10.3389","volume":"16","author":[{"given":"Jing-Jing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ting","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Li","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.cd004064","article-title":"Chemotherapy for advanced gastric cancer","volume":"8","author":"Wagner","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/b978-0-443-15609-0.00017-9","article-title":"Gastric cancer","volume":"396","author":"Smyth","year":"2020","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.21037\/jgo-23-464","article-title":"A narrative review of the evolving landscape of the management of metastatic gastric cancer: the role of targeted therapies","volume":"14","author":"Delgado-Ramos","year":"2023","journal-title":"J Gastrointest Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.gassur.2024.01.040","article-title":"Contemporary outcomes for resected type 1-3 gastroesophageal junction adenocarcinoma: a single-center experience","volume":"28","author":"Stiles","year":"2024","journal-title":"J Gastrointest Surg"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12041336","article-title":"Overview of chemotherapy for gastric cancer","volume":"12","author":"Sato","year":"2023","journal-title":"J Clin Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0115-y","article-title":"Fibroblast growth factor receptors as treatment targets in clinical oncology","volume":"16","author":"Katoh","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/s41392-020-00222-7","article-title":"FGF\/FGFR signaling in health and disease","volume":"5","author":"Xie","year":"2020","journal-title":"Signal Transduct Target Ther"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051201","article-title":"Fibroblast growth factor receptors (FGFRs) and noncanonical partners in cancer signaling","volume":"10","author":"Ferguson","year":"2021","journal-title":"Cells"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25020849","article-title":"Molecular targeting of the fibroblast growth factor receptor pathway across various cancers","volume":"25","author":"Shan","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B11","article-title":"Comprehensive identification of FGFR1-4 alterations in 5 557 Chinese patients with solid tumors by next-generation sequencing","volume":"11","author":"Gu","year":"2021","journal-title":"Am J Cancer Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.7150\/jca.29184","article-title":"Pathologic and prognostic impacts of FGFR2 amplification in gastric cancer: a meta-analysis and systemic review","volume":"10","author":"Kim","year":"2019","journal-title":"J Cancer"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2022.860985","article-title":"Signaling pathway and small-molecule drug discovery of FGFR: a comprehensive review","volume":"10","author":"Zheng","year":"2022","journal-title":"Front Chem"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2021.1837774","article-title":"Futibatinib, an investigational agent for the treatment of intrahepatic cholangiocarcinoma: evidence to date and future perspectives","volume":"30","author":"Rizzo","year":"2021","journal-title":"Expert Opin Investig Drugs"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2025.115262","article-title":"Phase 2 study of futibatinib in patients with gastric or gastroesophageal junction cancer harboring FGFR2 amplifications","volume":"218","author":"Satoh","year":"2025","journal-title":"Eur J Cancer"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-024-01466-w","article-title":"Bemarituzumab as first-line treatment for locally advanced or metastatic gastric\/gastroesophageal junction adenocarcinoma: final analysis of the randomized phase 2 FIGHT trial","volume":"27","author":"Wainberg","year":"2024","journal-title":"Gastric Cancer"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(23)00275-9","article-title":"Erdafitinib in patients with advanced solid tumours with FGFR alterations (RAGNAR): an international, single-arm, phase 2 study","volume":"24","author":"Pant","year":"2023","journal-title":"Lancet Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx107","article-title":"A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification","volume":"28","author":"Van Cutsem","year":"2017","journal-title":"Ann Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"431414367","DOI":"10.1177\/1758835920937889","article-title":"A phase II trial of the FGFR inhibitor pemigatinib in patients with metastatic esophageal-gastric junction\/gastric cancer trastuzumab resistant: the FiGhTeR trial","volume":"12","author":"Merz","year":"2020","journal-title":"Ther Adv Med Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdn717","article-title":"Capecitabine\/cisplatin versus 5-fluorouracil\/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial","volume":"20","author":"Kang","year":"2009","journal-title":"Ann Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s13691-024-00669-3","article-title":"A case of treatment-resistant advanced gastric cancer with FGFR2 gene alteration successfully treated with pemigatinib","volume":"13","author":"Shinomiya","year":"2024","journal-title":"Int Cancer Conf J"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyaf162","article-title":"Remarkable response of gastric adenocarcinoma with FGFR2-TRIM44 fusion to pemigatinib: a case report","volume":"56","author":"Fujiwara","year":"2026","journal-title":"Jpn J Clin Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(17)31827-5","article-title":"Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"390","author":"Kang","year":"2017","journal-title":"Lancet"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2013.48.8585","article-title":"Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial","volume":"31","author":"Li","year":"2013","journal-title":"J Clin Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.09.1439","article-title":"1527P Efficacy and safety of infigratinib in locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma patients with FGFR2 gene amplification","volume":"34","author":"Yuan","year":"2023","journal-title":"Ann Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.802","article-title":"FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study","volume":"110","author":"Su","year":"2014","journal-title":"Br J Cancer"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/s2468-1253(21)00196-5","article-title":"Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study","volume":"6","author":"Javle","year":"2021","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2024.103488","article-title":"An open-label study of pemigatinib in cholangiocarcinoma: final results from FIGHT-202","volume":"9","author":"Vogel","year":"2024","journal-title":"ESMO Open"},{"key":"B29","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1158\/2159-8290.cd-17-0395","article-title":"Genomic heterogeneity as a barrier to precision medicine in gastroesophageal adenocarcinoma","volume":"8","author":"Pectasides","year":"2018","journal-title":"Cancer Discov"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3892\/ijmm.2016.2620","article-title":"FGFR inhibitors: Effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review)","volume":"38","author":"Katoh","year":"2016","journal-title":"Int J Mol Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2478\/acph-2024-0005","article-title":"A comprehensive overview of selective and novel fibroblast growth factor receptor inhibitors as a potential anticancer modality","volume":"74","author":"Jain","year":"2024","journal-title":"Acta Pharm"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-16-0180","article-title":"Preclinical efficacy of the auristatin-based antibody-drug conjugate BAY 1187982 for the treatment of FGFR2-positive solid tumors","volume":"76","author":"Sommer","year":"2016","journal-title":"Cancer Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-024-00869-z","article-title":"FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions","volume":"21","author":"Katoh","year":"2024","journal-title":"Nat Rev Clin Oncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117745","article-title":"Discovery of LC-SF-14, a selective dual inhibitor of SHP2 and FGFR for the treatment of FGFR2-driven gastric cancer","volume":"294","author":"Zheng","year":"2025","journal-title":"Eur J Med Chem"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nature13480","article-title":"Comprehensive molecular characterization of gastric adenocarcinoma","volume":"513","year":"2014","journal-title":"Nature"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2015.3601","article-title":"Overexpression of FGFR2 contributes to inherent resistance to MET inhibitors in MET-amplified patient-derived gastric cancer xenografts","volume":"10","author":"Liu","year":"2015","journal-title":"Oncol Lett"},{"key":"B37","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13073-017-0447-8","article-title":"Linked read sequencing resolves complex genomic rearrangements in gastric cancer metastases","volume":"9","author":"Greer","year":"2017","journal-title":"Genome Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.mct-17-0367","article-title":"Acquired resistance to FGFR inhibitor in diffuse-type gastric cancer through an AKT-independent PKC-mediated phosphorylation of GSK3beta","volume":"17","author":"Lau","year":"2018","journal-title":"Mol Cancer Ther"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-19-0182","article-title":"TAS-120 overcomes resistance to ATP-competitive FGFR inhibitors in patients with FGFR2 fusion-positive intrahepatic cholangiocarcinoma","volume":"9","author":"Goyal","year":"2019","journal-title":"Cancer Discov"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1828167\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:23:33Z","timestamp":1783398213000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1828167\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":39,"alternative-id":["10.3389\/fonc.2026.1828167"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1828167","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"article-number":"1828167"}}