Selumetinib (3) – Koselugo®

• Clinical trials
  • The SPRINT trial is an ongoing, multicentre, open-label, single-arm Phase I/II trial.

Children aged 3 years and over and adolescents with symptomatic, inoperable plexiform neurofibromas (PN) associated with neurofibromatosis type 1 (NF1)

• Hint for a non-quantifiable additional benefit.
• Morbidity – change in volume of the target lesion
  • In the SPRINT trial, a reduction in the target lesion (best achieved percentage volume reduction) of -27% was demonstrated.
  • A reduction in volume was observed in 96% of patients.
  • Based on the statements made by the clinical experts during the oral hearing, it can be assumed that, given the current clinical presentation and stage of the disease, no spontaneous remissions occur during the natural course of the disease.
  • The volume of the PN represents the relevant severity of the disease and is the cause of any symptoms that may be present, including functional limitations, and may also be associated with disfigurement.
  • Due to the lack of a control group, the fundamental question initially arises as to the extent to which this represents an effect of the treatment.
  • The results are also subject to various other uncertainties: Firstly, due to the operationalisation of the endpoint, the effect of treatment with selumetinib on other existing plexiform neurofibromas that were not classified as target lesions is not recorded for the majority of study participants.
  • Furthermore, due to the absence of a control group, it is not possible to distinguish naturally occurring fluctuations (e.g. due to the tumour’s fluid content influenced by external factors) from changes observed since study enrolment.
• Conclusion
  • Given the available data, despite the single-arm study design, it is possible to infer an additional benefit of selumetinib for the treatment of children aged 3 years and over and adolescents with symptomatic, inoperable plexiform neurofibromas (PN) associated with neurofibromatosis type 1 (NF1).
  • Based on the comments of the clinical experts, it can be assumed that, given the current clinical presentation and stage of the disease, no spontaneous remissions occur during the natural course of the disease.
  • At the endpoints, therefore, despite remaining uncertainties, an improvement in therapeutic benefit can be observed for treatment with selumetinib in terms of a relevant reduction in tumour volume compared with baseline, indicating an advantage for selumetinib in the endpoint of change in tumour volume.
  • No suitable data are available for other patient-relevant endpoints in the categories of mortality, morbidity, quality of life and side effects due to the single-arm study design.
  • Consequently, it is not possible to weigh this against potential disadvantages in the overall assessment.
  • The extent of the additional benefit cannot therefore be quantified in light of the relevant limitations in the data.
• Overall assessment
  • In the overall assessment, a non-quantifiable additional benefit is identified for selumetinib.

Courtesy translation only, please refer to the German original.