Case report: Complete and durable response to larotrectinib (TRK inhibitor) in an
infant diagnosed with angiosarcoma harbouring a KHDRBS1-NTRK3 fusion gene
(739593 (European Union’s Horizon 2020 Research and Innovation Programme))
Significant improvements in the survival rates of paediatric cancer have been achieved
over the past decade owing to recent advances in therapeutic and diagnostic strategies.
However, disease progression and relapse remain a major challenge for the clinical
management of paediatric angiosarcoma. Comprehensive genomic profiling of these rare
tumours using high-throughput sequencing technologies may improve patient stratification
and identify actionable biomarkers for therapeutic intervention. Here, we describe
the clinical, histopathological, immunohistochemical and molecular profile of a novel
and precision medicine-informed case where a KHDRBS1-NTRK3 fusion determined by next-generation
sequencing-based comprehensive genomic profiling led to complete and sustained remission
(clinical and radiological response) in an otherwise incurable disease. Our patient
represents the first paediatric angiosarcoma harbouring a targetable NTRK3 fusion
in the literature and demonstrates the first example of targeting this alteration
in angiosarcoma using larotrectinib, an NTRK inhibitor. Clinical and radiological
remission was achieved in under two months of therapy, and the patient is currently
in complete remission, 4 month after stopping larotrectinib therapy, which was given
over 17 months with only mild side effects reported. Therefore, this remarkable case
exemplifies the true essence of precision-based care by incorporating conventional
pathology with the why, when, and how to test for rare oncogenic drivers and agnostic
biomarkers in paediatric angiosarcoma.