Precision medicine: Sustained response to erdafitinib in FGFR2-mutant, multiply recurrent ameloblastoma

Background: Ameloblastoma imposes significant morbidity and high-recurrence rates following surgery and radiation therapy. Although 89% of cases harbor oncogenic mutations, the role of targeted therapy is undefined. Case: We describe a case of a 40-year-old male with multiply recurrent, locally invasive ameloblastoma of the posterior maxillary ridge. The tumor was unresectable for negative margins due to extensive intracranial disease, and the patient suffered severe symptoms including pain. Immune and genomic profiling were obtained to guide systemic treatment, showing a PD-L1 score of 2% and FGFR2^V395D and SMO^W535L mutations. The patient progressed rapidly on anti-PD1 immunotherapy. He was treated with the FGFR inhibitor, erdafitinib, with excellent partial response including resolution of intracranial disease and cancer-related pain, ongoing 2 years after drug initiation. Conclusion: Targeting the FGFR2 mutation resulted in sustained response and improved quality of life. Genomic profiling with targeted therapy for ameloblastoma appears promising, especially when surgery is technically infeasible.