Nat Med: The efficacy of cabozantinib for clump neurofibromatosis

Of the approximately 7,000 known rare diseases, less than 10% have treatments available or are under development.
one of the most common of these rare diseases is neurofibromatosis type 1 (NF1), a tumour-prone syndrome caused by the loss of function of the NF1 tumor suppressor gene.
abnormal neurofibrin causes the activation of the component p21Ras, leading to the occurrence of tumors of the central and peripheral nervous systems.
the development of NF1 treatments remains challenging due to the heterogeneity of the disease, the small number of patients and geographical dispersion.
plexual neurofibromatosis (PNs) is one of the most common and affecting clinical manifestations of NF1.
PNs is an aggressive multicellular tumor that can cause disease and may turn into sarcoma.
previous studies have shown that treating Nf1fl/fl mice with a variety of tyrosine kinase inhibitors, cabozantinib, leads to a decrease in PN size and number, as well as differences in kinase regulation in cell lineages that drive PN growth.
Cabotinib reduces the PN tumor burden in NF1 mutant mice In light of these findings, the Neurofibromatosis Clinical Trial Alliance conducted a multi-center Phase 2 clinical trial (NCT02101736) for adolescent and adult NF1 and non-removable, reactive or symptomatic PNs to assess Cabotinib's safety, efficacy, and biological activity.
results showed that the main outcome of the trial was that more than 25 percent of patients achieved partial remission after 12 courses of treatment (PR, reduced body volume ≥20 percent) of the target lesions assessed by magnetic resonance imaging (MRI).
secondary outcomes of the trial include adverse events (AEs), patient reports assessing pain and quality of life (QOL), pharmaconomics (PK), and levels of circulating endodermic cells and cytokines.
clinical trial flowchart reached partial remission (PR) in 8 (42%) of the 19 assessable participants.
change in tumor volume was 15.2% (ranging from +2.2% to -36.9%), and there was no exacerbation of the disease during treatment.
further studies showed that nine of the patients needed to reduce the dose of the drug or discontinue treatment due to adverse events, such as gastrointestinal toxicity, hypothyroidation, fatigue and PPA (palmar plantar erythrodysesthesia).
11 level 3 adverse events occurred in 8 patients.
found that the intensity of tumor pain and pain interference in daily life decreased significantly in PR patients, but overall QOL scores did not change.
patients' reactions to cabotinib, the results showed that cabotinib was active in NF1-related PNs, which can lead to reduced tumor volume and improved pain in patients.