not-yet-known
      not-yet-known
    
    
      not-yet-known
      
      
        unknown
      
    
  
  
    Larotrectinib
    Larotrectinib, also known as LOXO-101, is an orally administered
inhibitor that targets TRKA, TRKB, and TRKC, with a 50% inhibitory
concentration (IC50) of 5–11 nM in vitro, and its sensitivity for TRK
exceeds 100 times over other kinases.(22) Larotrectinib has been shown
to be clinically active in infants, children, adolescents adult patients
with TRK fusion-positive cancers.(22–24) In this case, Larotrectinib
allowed for a decrease in tumor size, and improvements of the symptoms.
This case report demonstrates the potential of targeted therapies in
selected pediatric patients with unique oncogenic drivers for which
specific inhibitors are available. Our patient presented with back pain
and lower limb weakness that improved after initiation of Larotrectinib
in addition to dexamethasone. It is worth mentioning that there was a
one-time deterioration following the discontinuation of Larotrectinib.
    In ½ phase clinical trial studying the use of Larotrectinib in pediatric
NTRK fusion-positive solid tumors, patients received larotrectinib
orally, either in capsule or liquid form, twice daily In 28-day cycles
of continuous dosing. For patients with locally advanced sarcomas,
surgical intervention was an option after achieving a satisfactory
response to the treatment. Patients with no residual tumor at the
resection margin (UICC-R0) were able to discontinue larotrectinib and
undergo regular radiographic imaging every 3 months. Patients with
marginal (R1) or gross residual (R2) surgery were eligible to resume
larotrectinib immediately after the surgery. Patients who showed a
positive response to larotrectinib were allowed to enter a ”wait and
see” period, during which the drug was discontinued for a minimum of six
treatment cycles. If disease progression occurred after drug
discontinuation, retreatment with larotrectinib was possible.(23)
    In our case report, we followed the recommendation of phase ½ clinical
trial for the dose of Larotrectinib which is 100mg maximum per dose,
though, it was for ten months. The Larotrectinib started after five
months of the last spinal tumor resection.
    On the other hand, several cases with NTRK-fusions demonstrated
promising results in disease control with targeted therapy and long-term
survival. Specifically, a number of LGGs cases showed clinical benefits
evidenced by MRI. (19,20,25) Moreover, high efficacy in multiple
NTRK-driven cancers is shown by the use of NTRK inhibitors (e.g.
Larotrectinib).(26)
    Regarding the adverse events of Larotrectoinib, patients with solid
tumors experienced various adverse events, including increased levels of
liver enzymes (ALT or AST), fatigue, vomiting, dizziness, nausea,
anemia, diarrhea, constipation, cough, weight gain, shortness of breath,
headache, fever, joint pain, back pain, and decreased neutrophil count,
thrombocytopenia, bleeding, and anemia.(10,22–24,27)