Predictive significance of FGFR4 p.G388R polymorphism in metastatic colorectal cancer patients receiving trifluridine/tipiracil (TAS-102) treatment

• DOI: 10.1186/s12967-024-05184-w
• Publication Date: 2024-04-22T19:01:32Z
• Authors: Alessandro Ottaiano; Mariachiara Santo...; Monica Ianniello; Anna Ceccarelli; Marika Casillo; Francesco Sabbatino; Nadia Petrillo; Marco Cascella; Francesco Caraglia; Carmine Picone; Francesco Perri; Roberto Sirica; Silvia Zappavigna; Guglielmo Nasti; Giovanni Savarese; Michele Caraglia
• Keywords: Performance status

Abstract Background TAS-102 (Lonsurf ® ) is an oral fluoropyrimidine consisting of a combination trifluridine (a thymidine analog) and tipiracil phosphorylation inhibitor). The drug effective in metastatic colorectal cancer (mCRC) patients refractory to fluorouracil, irinotecan oxaliplatin. This study real-world analysis, investigating the interplay genotype/phenotype relation sensitivity. Methods Forty-seven consecutive mCRC were treated with at National Cancer Institute Naples from March 2019 2021, dosage 35 mg/m 2 , twice day, cycles 28 days (from day 1 5 8 12). Clinical-pathological parameters described. Activity was evaluated RECIST criteria (v1.1) toxicity NCI-CTC (v5.0). Survival depicted through Kaplan-Meyer curves. Genetic features Next Generation Sequencing (NGS) Illumina NovaSeq 6000 platform TruSigt™Oncology 500 kit. Results Median age 65 years (range: 46–77). Forty-one had or more sites 38 underwent than previous lines therapies. ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) 19 patients. median number 4 2–12). most frequent toxic event neutropenia (G3/G4 16 patients). There no severe (> 3) non-haematological toxicities treatment-related deaths. Twenty-six experienced progressive disease (PD), 21 stable (SD). Three long-lasting control (DC: complete, partial responses disease) shared FGFR4 (p.Gly388Arg) mutation. Patients experiencing DC frequently low tumour growth rate ( P = 0.0306) p.G388R variant < 0.0001). Arg388 genotype associated better survival (median: 6.4 months) compared Gly388 months); HR 0.25 (95% CI 0.12- 0.51; 0.0001 Log-Rank test). Conclusions phenotype/genotype investigation suggests that may serve as new marker for identifying who are responsive TAS-102. A mechanistic hypothesis proposed interpret these findings. Graphical