Clinical Response to Futibatinib in Patients with High-Level FGFR2-Amplified Advanced Gastric Cancer: Two Case Reports

• Published in: Clinical drug investigation Vol. 42; no. 8; pp. 697 - 701
• Main Authors: Quinzii, Alberto, Zecchetto, Camilla, Casalino, Simona, Gaule, Marina, Pesoni, Camilla, Merz, Valeria, Contarelli, Serena, Pietrobono, Silvia, Benhadji, Karim A., Melisi, Davide
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-08-2022; Springer Nature B.V
• Subjects: Abdomen; Cancer therapies; Case reports; Chemotherapy; Family medical history; Fibroblasts; Gastric cancer; Gastrointestinal surgery; Growth factors; Internal Medicine; Intestinal obstruction; Kinases; Ligands; Liver; Medicine; Medicine & Public Health; Metastasis; Monoclonal antibodies; Mutation; Pain; Patients; Pharmacology/Toxicology; Pharmacotherapy; Research Letter; Tumors
• ISSN: 1173-2563; 1179-1918
• DOI: 10.1007/s40261-022-01183-1

Genomic alterations responsible for a ligand-independent activation of these tyrosine kinases receptors, including activating point mutations, amplifications, or chromosomal translocations/fusions, contribute to malignant transformation by enhancing cellular proliferation, migration, survival, and angiogenesis [6]. According to the Cancer Genome Atlas Research Network molecular classification data, the amplification of the gene coding for FGFR2 is one of the most frequent molecular alterations in gastric cancer, identified in 9% of the overall population. Nonetheless, early-phase clinical trials with ATP-competitive FGFR kinase inhibitors in gastric cancer patients showed that the clinical benefit might be limited to those 5% of patients with a homogeneously high-level (FGFR2/chromosome 10 probe ratio > 5) clonal FGFR2amplification [7]. Treatment with bemarituzumab (first-in-class humanized IgG1 monoclonal antibody selective for fibroblast growth factor receptor 2b) in combination with chemotherapy was found to improve overall survival (OS) in patients with FGFR2bpositive, human epidermal growth factor receptor 2 (HER2)negative frontline advanced gastric or gastroesophageal junction cancers.