Larotrectinib (1) – Vitrakvi®

• Clinical trials
  • The NAVIGATE trial is a Phase II, uncontrolled clinical study that has been ongoing since October 2015.
  • The LOXO-TRK-14001 trial is a Phase I, uncontrolled clinical study that has been ongoing since May 2014.
  • The SCOUT trial is a Phase I, open-label, multicentre dose-escalation and expansion clinical study that has been ongoing since December 2015.

Adult and paediatric patients with solid tumours harbouring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have locally advanced or metastatic disease, or a condition where surgical resection has a high probability of resulting in severe morbidity, and for whom no satisfactory treatment options are available

• An additional benefit of larotrectinib over the appropriate comparator therapy is not proven.
• Consequently, the evidence presented does not allow for a comparison with the appropriate comparator therapy, which is why an additional benefit of larotrectinib is not proven.
• Conclusion
  • For the benefit assessment, the pharmaceutical manufacturer has submitted the results from the NAVIGATE, LOXO-TRK-14001 and SCOUT registration trials, as well as pooled data on patients with NTRK gene fusions from these trials, relating to treatment with larotrectinib.
  • The therapeutic indication for larotrectinib covers various tumour entities and, consequently, tumour diseases with different courses and prognoses. The G-BA therefore considers it appropriate and necessary to assess the results separately for each tumour entity.
  • All three registration studies are uncontrolled clinical studies and therefore do not include a control group. Similarly, the submitted analyses of the pooled data do not include a control group.
  • Overall, the evidence submitted by the pharmaceutical manufacturer to demonstrate additional benefit lacks a comparison with the appropriate comparator therapy.
  • Although the pharmaceutical manufacturer has submitted analyses of the results of treatment with larotrectinib, it has not carried out a comparison with the appropriate comparator therapy, either for the pooled data or for the data on individual tumour entities.
  • Consequently, the evidence submitted does not allow for a comparison with the appropriate comparator therapy, which is why no additional benefit of larotrectinib as monotherapy can be established for the treatment of adult and paediatric patients with solid tumours harbouring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have locally advanced or metastatic disease or a condition in which surgical resection has a high probability of resulting in severe morbidity, and for whom no satisfactory treatment options are available, is not proven.

Courtesy translation only, please refer to the German original.