Clinical response to FGFR inhibitors in patients with FGFR2-amplified advanced gastric cancer: two case reports

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 = 2) 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 = 5) 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.